| Objective1. To observe and summarize the TCM clinical syndrome features of the patients with MetS and microalbuminuria（MAU） under the guidance of "Aggregation syndrome theory" and the theory "analogous patterns in the same disease".2. To investigate the efficacy of Yiqi Huaju Qingli Herb Formula on microalbuminuria with metabolic syndrome when it is combined with routine western medicine treatment and to analyze the relationship between the improvement on insulin resistance and rectification of abnormal fat distribution.3. To investigate the effects of Yiqi Huaju Qingli Herb Formula on the cases of the MetS component diseases and the cases of MetS components of the patients with MetS and MAU when it is combined with routine western medicine treatment.4. To investigate the effects of Yiqi Huaju Qingli Herb Formula on clinical symptoms of the patients with MetS and MAU when it is combined with routine western medicine treatment.5. To investigate the possible mechanism of Yiqi Huaju Qingli Herb Formula on the patients with MetS and MAU focused on regulating levels of adipokines. inflammatory cytokines, prothrombotic factors. Oxidative stress molecules and markers of vasoreactivityMethods1. Features of TCM clinical syndrome of the patients with MetS and MAU100patients were recruited from the department of Integrative Medicine at Huashan Hospital, Fudan University and the department of endocrinology at Yueyang Integrative Medicine Hospital, Shanghai University of Traditional Chinese Medicine. Initial screening included a medical history, physical examination and the frequency of different TCM clinical symptoms was also recorded in order to summarize the TCM clinical syndrome features of the patients with MetS and MAU under the guidance of "Aggregation syndrome theory" and the theory "analogous patterns in the same disease".2. Investigation of the efficacy of Yiqi Huaju Qingli Herb Formula on microalbuminuria with metabolic syndrome when it is combined with routine western medicine treatment100patients aboved were randomly divided into Chinese herb formula group （CHF, Yiqi Huaju Qingli formula treatment in combination with western medicine, n=50） and control groupplacebo in combination with western medicine, n=50. Both kinds of treatment were administered for12weeks. Urinary microalbumin, Urinary albumin-to-creatinine ratio（UACR）,24hours urinary total protein（24hTP）, urine transferrin, urinary beta2-microglobulin, body mass index （BMI）, waist circumference（WC）. waist/hip ratio（WHR）, Homeostasis model assessment of insulin resistance（HOMA-IR）, fasting plasma glucose （FPG）,2h postprandial plasma glucose （2hPPG）, glycosylated hemoglobin （HbAlc）, fasting plasma insulin （FPI）, Total cholesterol （TC）, Triglycerides （TG）. high-density lipoprotein （HDL）, low-density lipoprotein （LDL）. systolic pressure （SBP）. diastolic pressure （DBP） were observed between two groups. Efficacy and conversion rate of MAU between the two groups were observed. The cases of the MetS component diseases, the cases of MetS components of the patients with MetS and the average cases of MetS components were also observed. TCM syndrome score was observed in addition to the efficacy of TCM clinical symptoms.3. Investigation of the the possible mechanism of Yiqi Huaju Qingli Herb Formula on microalbuminuria with metabolic syndromeBlood was drawn from the above MAU patients with metabolic syndrome to measure the levels of serum adiponectin, leptin, hs-CRP, TNF-a. IL-6, MCP-1, ADM A, plasma PAI-1, t-PA, fibrinogen, ICAM-1, VCAM-1, NO, ET-1,6-k-PGF1α,8-isoPGF2a. The above cytokines were compared before and after treatment in the two groups.The correlations between the percentage change in UACR and the percentage changes in other related parameters in patients of CHF group and the correlations between the percentage change in UACR and the percentage change in the above cytokines were analyzed with simple and multiple linear regression analysis respectively.Results1. Features of TCM clinical syndrome of the patients with MetS and MAUIn the100patients with MetS and MAU, the most frequent clinical symptoms were obesity, heaviness in the body, shortness of breath and lassitude, spontaneous perspiration, mass and fullness in epigastrium. Other clinical symptoms were thirst to drink, Bubbles in urine, waist sour, numbness in the body, bitter taste in the mouth, dizziness and so on. Tongue bodies were red, or dark and enlarged with tooth dent in the margins. Tongue coatings included white greasy coating, yellow greasy coating, thick greasy coating and so on. Pulses were wiry, wiry and rapid, slippery, thready and rapid, soft and thready, deep and so on.2. Efficacy of Yiqi Huaju Qingli Herb Formula on microalbuminuria with metabolic syndrome1) Comparison of BM1, waist circumference, and WHR before and after treatment in the two groupsThere was no significant change in terms of BMI, waist circumference and waist/hip in control group after treatment （p>0.05）. In contrast, significant decrease in BMI. waist circumference and waist/hip ratio were observed in CHF group after treatment（p<0.01）. Significantly decreased BMI （p<0.05）, waist circumference （p<0.01） and waist/hip ratio （p<0.01）were also noted in CHF group compared to that from control group after both treatments. For further analysis of waist circumference and waist-to-hip ratio of males and females respectively, there was no significant change in terms of waist circumference and waist/hip of both males and females in control group after treatment （p>0.05）. In contrast, significant decrease in waist circumference and waist/hip ratio of both males and females were observed in CHF group after treatment（p<0.01）. Significantly decreased waist circumference （p<0.01） and waist/hip ratio of both males and females （p<0.01）were also noted in CHF group compared to that from control group after both treatments. Significant reduction in HOMA-IR were recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of HOMA-IR after treatment（p<0.05）.2) Comparison of FPG,2hPPG, HbAlc before and after treatment in the two groups Significant reduction in FPG,2hPPG and HbAlc were recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of FPG,2hPPG and HbAlc after treatment （p<0.05）.3) Comparison of TC, TG, LDL-C and HDL-C before and after treatment in the two groupsBoth CHF and control treatment displayed a significant effect on reducing the level of TC, TG and LDL-C, respectively （p<0.01）. A more significant reduction of TG was observed after CHF treatment compared to that from control treatment （p<0.05）. The level of HDL-C was not altered significantly in control group after treatment（p>0.05）, whereas it was significantly increased by CHF treatment （p<0.01）, although there was no significant difference of HDL-C in CHF group compared to that from the control group after treatment（p>0.05）. For further analysis of TG-to-HDL ratio, both CHF and control treatment displayed a significant effect on reducing the level of TG-to-HDL ratio respectively （p<0.01）. A more significant reduction of TG-to-HDL was observed after CHF treatment compared to that from control treatment （p<0.05）.4) Comparison of urinary MA, UACR,24hTP, urine transferrin and urinary beta2-microglobulinbody before and after treatment in the two groupsBoth CHF and control treatment displayed a significant effect on reducing the level of MA, UACR and urinary beta2-microglobulinbody respectively（p<0.05, P<0.01）. The reductions of MA, UACR and urinary beta2-microglobulinbody in CHF group were much greater compared to control group （p<0.05）. The level of24hTP was not altered significantly by control treatment （p>0.05）, whereas it was significantly decreased by CHF treatment （p<0.01）. There was significant difference of24hTP in CHF group compared to that from the control group after treatment （p<0.05）.5) Comparison of SBP, DBP and MBP before and after treatment in the two groupsCompared to that before the treatment, significant decrease in SBP, DBP and MBP were observed in both CHF group and control group （p<0.01）. CHF treatment resulted in a greater reduction in SBP and MBP compared to that from the control treatment （p<0.05, P<0.01）. However, there was no significant difference between two groups in DBP（p>0.05）.6) Comparison of the efficacy of MAU between the two groups after treatmentAmong50patients in the CHF group,26patients reached the standard of significant effectiveness,12patients reached the standard of effectiveness,12patients reached the standard of ineffectiveness and the total percentage rate of effectiveness reached76.0%. While in the control group,16patients reached the standard of significant effectiveness,7patients reached the standard of effectiveness,27patients reached the standard of ineffectiveness and the total percentage rate of effectiveness reached only46.0%. The total percentage rate of effectiveness was higher in the CHF group than that in the control group（x2=9.466, P<0.01）.7) Comparison of the conversion rate of MAU between the two groups after treatmentAmong50patients in the CHF group,14patients reached the standard of normicroalbuminuria,33patients maintained the standard of microalbuminuria,3patients reached the standard of macroalbuminuria. While in the control group,5patients reached the standard of normicroalbuminuria,40patients maintained the standard of microalbuminuria,5patients reached the standard of macroalbuminuria. The total negative conversion percentage rate of MA was higher in the CHF group than that in the control group（x2=10.048, P<0.01）.8) Comparison of the uncontrolled cases of the MetS component diseases between the two groups before and after treatmentThe occurrence of central obesity, high TG, low HDL, uncontrolled hypertension and uncontrolled diabetes was decreased in CHF group compared to that from the control group after treatment. Among all these component diseases of MetS, the occurrence of central obesity was decreased by58%. uncontrolled hypertension by58%and uncontrolled diabetes by20%. The occurrence of central obesity, uncontrolled hypertension and uncontrolled diabetes showed a significant difference between CHF and control group.（p<0.05, P<0.01）.9) Comparison of the the cases of MetS components and average MetS components before and after treatment in the two groupsThe number of MetS components was decreased in both CHF and control groups after treatment. None of the patients displayed the coexistence of5MetS components after CHF treatment. Patients with4MetS components were evidently decreased after CHF treatment.2patients were characterized by0MetS components after CHF treatment. However, there were5patients exhibiting5MetS components after control treatment and no patient was identified with0MetS component. The average number of MetS component was decreased from4.08±0.76prior to the treatment to2.62±0.86after the treatment in the CHF group （p<0.01）. In the control group, the average number was3.47±0.84after the treatment compared to4.15±0.75before the treatment （p<0.01）. The average number of MetS after CHF treatment was significantly lower than that after the control treatment （p<0.01）.10) Comparison of the main symptom scores of TCM between the two groups before and after treatmentThere was no significant change in terms of the main symptom scores of TCM in control group after treatment （p>0.05）. In contrast, significant decrease in the main symptom scores of TCM were observed in CHF group after treatment（p<0.01）. Significantly decreased main symptom scores of TCM were also noted in CHF group compared to that from control group after both treatments（P<0.01）.11) Comparison of the the efficacy of main symptoms of TCM between the two groups before and after treatmentThe total percentage rate of the efficacy of main symptoms of TCM reached78.0%in the CHF group. While in the control group, the total percentage rate of the efficacy of main symptoms of TCM reached only13.2%. The total percentage rate of the efficacy of main symptoms of TCM was higher in the CHF group than that in the control group （x2=16.99. P<0.001）.3. Investigation of the the possible mechanism of Yiqi Huaju Qingli Herb Formula on microalbuminuria with metabolic syndrome3.1Effects of Yiqi Huaju Qingli Herb Formula on serum levels of adipokines and inflammatory cytokines1) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of adiponectinThere was no significant change in terms of adiponectin in control group after treatment compared to that before the treatment （p>0.05）. In contrast, significant increase in adiponectin was observed in CHF group after treatment compared to that before the treatment （p<0.01）. Significantly increased adiponectin was also noted in CHF group compared to that from control group after both treatments（P<0.05）.2) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of leptinSignificant reduction in leptin was recorded in both CHF and control groups after treatment （p<0.05. P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of leptin （p<0.01）.3) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of hs-CRPSignificant reduction in hs-CRP was recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of hs-CRP （p<0.05）.4) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of TNF-αSignificant reduction in TNF-a was recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of TNF-α（p<0.05）.5) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of IL-6There was no significant change in terms of IL-6in control group after treatment compared to that before the treatment （p>0.05）. In contrast, significant decrease in IL-6was observed in CHF group after treatment compared to that before the treatment （p<0.01）. Significantly decreased IL-6was also noted in CHF group compared to that from control group after both treatments（P<0.01）.6) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of MCP-1Significant reduction in MCP-1was recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of MCP-1（p<0.05）.3.2Effects of Yiqi Huaju Qingli Herb Formula on plasma levels of prothrombotic factors1) Effects of Yiqi Huaju Qingli Herb Formula on plasma levels of PAI-1There was no significant change in terms of PAI-1in control group after treatment compared to that before the treatment （p>0.05）. In contrast, significant decrease in PAI-1was observed in CHF group after treatment compared to that before the treatment （p<0.01）. Significantly decreased PAI-1was also noted in CHF group compared to that from control group after both treatments（P<0.05）.2) Effects of Yiqi Huaju Qingli Herb Formula on plasma levels of t-PAThere was no significant change in terms of t-PA in control group after treatment compared to that before the treatment （p>0.05）. In contrast, significant increase in t-PA was observed in CHF group after treatment compared to that before the treatment （p<0.01）. Significantly increased t-PA was also noted in CHF group compared to that from control group after both treatments（P<0.05）.3) Effects of Yiqi Huaju Qingli Herb Formula on plasma levels of fibrinogenThere was no significant change in terms of fibrinogen in control group after treatment compared to that before the treatment （p>0.05）. In contrast, significant increase in fibrinogen was observed in CHF group after treatment compared to that before the treatment （p<0.01）. Significantly decreased fibrinogen was also noted in CHF group compared to that from control group after both treatments（P<0.05）.3.3Effects of Yiqi Huaju Qingli Herb Formula on serum levels of adhesion molecules1) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of ICAM-1Significant reduction in ICAM-1was recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of ICAM-1（p<0.05）.2) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of VCAM-1Significant reduction in VCAM-1was recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of VCAM-1（p<0.05）.3.4Effects of Yiqi Huaju Qingli Herb Formula on levels of markers of vaso reactivity1) Effects of Yiqi Huaju Qingli Herb Formula on plasma levels of NOSignificant increase in NO was recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on increasing the level of NO （p<0.05）.2) Effects of Yiqi Huaju Qingli Herb Formula on plasma plasma of ET-1Significant reduction in ET-1was recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of ET-1（p<0.05）.3) Effects of Yiqi Huaju Qingli Herb Formula on serum levels of ADMA Significant reduction in ADMA was recorded in both CHF and control groups after treatment （p<0.05, P<0.01）. When these parameters were compared between CHF group and control group, the former showed a statistically greater effects on reducing the level of ADMA （p<0.05）.3.5Effects of Yiqi Huaju Qingli Herb Formula on plasma levels of Oxidative stress markers1) Effects of Yiqi Huaju Qingli Herb Formula on plasma levels of6-k-PGF1αThere was no significant change in terms of6-k-PGF1α in control group after treatment compared to that before the treatment （p>0.05）. In contrast, significant increase in6-k-PGF1α was observed in CHF group after treatment compared to that before the treatment （p<0.01）. Significantly increased6-k-PGF1α was also noted in CHF group compared to that from control group after both treatments（P<0.05）.2) Effects of Yiqi Huaju Qingli Herb Formula on plasma levels of8-isoPGF2aThere was no significant change in terms of8-isoPGF2a in control group after treatment compared to that before the treatment （p>0.05）. In contrast, significant reduction in8-isoPGF2a was observed in CHF group after treatment compared to that before the treatment （p<0.01）. Significantly decreased8-isoPGF2a was also noted in CHF group compared to that from control group after both treatments（P<0.05）.3.6Pearson rank correlation between the percentage change in UACR and the percentage changes in other related parameters in participants of CHF groupOn univariate analysis, the percentage change in UACR was correlated with percentage changes in WC （r=0.691, P<0.001）, WHR （r=0.677, P<0.001） and HOMA-1R （r=0.502, P<0.001）. The percentage change in UACR was also correlated with percentage changes in SBP （r=0.617, P<0.001）. FPG （r=0.344. P<0.05）. PPG （r=0.494, P<0.001） and HbAlc （r=0.477. P<0.001）.With respect to adipokines and inflammatory cytokines. the percentage change in UACR was correlated with percentage changes in adiponectin （r=-0.724, P<0.001）. leptin （r=0.501, P<0.001）, TNF-a （r=0.590, P<0.001）. In terms of markers of vasoreactivity, the percentage change in UACR was correlated with percentage changes in NO （r=-0.580. P<0.001）, ET-1（r=0.366, P<0.01）, ADMA （r=0.680. P<0.001）.In stepwise multiple regression analysis using the above parameters as independent variables, only percentage changes in adiponectin （standard coefficient=-0.626, P<0.001） and leptin （standard coefficient=0.291, P<0.01） were significantly and independently correlated with percentage change in UACR （r=0.60. P<0.01）.Conclusions1. The TCM pattern of the patients with metabolic syndrome and microalbuminuria can be classified as the analogous pattern of "Aggregation syndrome" which holds that when the patients develop MAU, the "evil heat" and "evil wet" would damage the kidney and the blood stasis would block the collateral pathway.2. Combined treatment of Yiqi Huaju Qingli herb formula and routine western medicine significantly alleviated microalbuminuria, which was superior to routine western medicine itself.3. Combined treatment of Yiqi Huaju Qingli herb formula and routine western medicine exerted multifactorial intervention on a variety of cardiovascular risk factors in metabolic syndrome in addition to further controlling glucose, blood pressure, lipid profiles and effectively improving the clinical symptoms.4. Amelioration of microalbuminuria with treatment of Yiqi Huaju Qingli herb formula was closely related to the improvement on insulin resistance and rectification of abnormal fat distribution.5. Yiqi Huaju Qingli herb formula ameliorated microalbuminuria, promoted functional activity of qi and dissipated aggregation of pathogenic factors through possible mechanisms which include regulation of levels of adipokines, inflammatory cytokines, prothrombotic factors, Oxidative stress molecules and markers of vasoreactivity. |
PDF Full Text Request