| Objective:According to Damp-heat syndrome is closely related to infection in primary nephrotic syndrome (PNS), Damp-heat and infection have a similar pathological effects on PNS such as relapse, condition deteriorated and persistent, and some of our pre-clinical research, this study presents a hypothes that PNS Damp-heat syndrome may be related with inflammatory cytokines. We chose PNS Damp-heat syndrome patients as research objects, systematically collected PNS cases nearly 6 years in our hospital, observed Damp-heat syndrome incidence rate, the impact of Damp-heat factor on PNS conditions and infection rate in Damp-heat syndrome cases, in order to provide a theoretical basis for clinical treatment of strengthening clearing away heat and draining dampness and improve therapeutic efficacy. Further the correlation between PNS Damp-heat syndrome and pro-inflammatory cytokines was studied to systemicly and thoroughly investigate the relevance of PNS Damp-heat syndrome and pro-inflammatory factors, reveal the nature of PNS damp-heat syndrome and the pathogenesis, and promote the diagnosis of PNS Damp-heat syndrome standardized and objective.Methods:Using cross-sectional, prospective, retrospective study methods, we collected PNS cases met the inclusion criteria from 2004.1 to 2010.1 in our hospital, investgated the patients in general, symptoms, signs, and some laboratory indicators, counted the incidence of Damp-heat syndrome, analyze the influence of Damp-heat on patient's condition, and correlation between Damp-heat syndrome and infection. Then using prospective, randomized controlled clinical research methods, we selected 40 Damp-heat syndrome cases and 20 non Damp-heat syndrome cases, observed the difference between the two groups in serum hs-CRP, IL-6, NF-κB and urine MCP-1 levels; again the Damp-heat syndrome group was randomly divided into control group and Huangkui Capsule treatment group,20 patients in each, compared the changes of pro-inflammatory cytokines and Damp-heat syndrome in each group before and after treatment, overall evaluated the correlation between pro-inflammatory cytokines and Damp-heat syndrome.Result:㈠The correlational study between PNS Damp-heat syndrome and infection1. The comparison of PNS syndrome compositionThis study included 290 cases, in which Damp-heat syndrome group 118 cases (40.69%), deficiency of spleen and kidney yang syndrome group 43 cases (14.83%), asthenia of spleen and kidney qi syndrome group 46 cases (15.86%), deficiency of both qi and yin syndrome group 33 cases (11.38%), the other syndrome group 50 cases (17.24%). Damp-heat syndrome incidence was significantly higher than that Damp-heat syndrome in PNS cases.2. The comparison of age among all syndrome groups suffer from PNSThe age of Damp-heat syndrome group was 26.36±10.80 years old, which is significantly younger than that of the other four non Damp-heat syndrome groups, by statistical tests, there were significant difference (p<0.05, p<0.01)).3. The comparison of renal biopsy type among groups133 of 290 PNS cases had renal biopsy reports, accounting for 45.86% of total cases. The main pathological types in each group:Damp-heat syndrome group included 19 cases(35.85%) of Glomerular minor lesion,16 cases(30.19%) of Mesangial proliferative glomerulonephritis, deficiency of spleen and kidney yang syndrome group included 7 cases (35.0%, respectively) of Mesangial proliferative glomerulonephritis and Membranous nephropathy respectively, asthenia of spleen and kidney qi syndrome group contained 7 cases (36.84%) of Minimal change nephropathy, deficiency of both qi and yin syndrome group included 6 cases (28.57%, respectively) of Glomerular minor lesion and Mesangial proliferative glomerulonephritis respectively, the other syndrome group contained 8 cases (40.0%) of Mesangial proliferative glomerulonephritis. In each group there were few renal biopsy to be statistically analyzed.4. The comparison of laboratory indicators among PNS syndrome groupsThe total number of neutrophils (7.94±4.79)×10e9/L, neutrophil percentage (69.78±14.05)%, urinary protein (7.42±3.59) g/24h of Damp-heat syndrome group were significantly higher, compared with those of deficiency of spleen and kidney yang syndrome group, asthenia of spleen and kidney qi syndrome group, deficiency of both qi and yin syndrome group and the other syndrome group. By statistical tests, there were significant difference (P<0.05, P<0.01). The serum total protein (38.09±6.77)g/L, albumin (17.19±5.68)g/L of Damp-heat syndrome group were obviously lower than those of the other four groups, the serum total cholesterol (11.50±3.63)mmol/L, low density lipoprotein (7.85±2.99) mmol/L of Damp-heat syndrome group were significantly higher than those of the other four groups, by statistical tests, there were statistical significance (P<0.05, P<0.01).5. The relationship between Damp-heat syndrome and infectionIn all 290 PNS patients there were 124 infection cases (42.76%). The infection rate in Damp-heat syndrome group (59.3%) was significantly higher than in deficiency of spleen and kidney yang syndrome group (41.9%), asthenia of spleen and kidney qi syndrome group(23.9%), deficiency of both qi and yin syndrome group(12.1%) and the other syndrome group(42.0 %).By statistical tests, there were significant differences (P<0.05, P<0.01).Infection sites in each group:Damp-heat syndrome group includes 55 cases (78.57%) of respiratory infection,11 cases of skin infection (15.71%), 4 cases of urinary tract and gastrointestinal infection each (5.71%, respectively),2 cases of other infection sites (2.86%),6 cases of two or more infection sites (8.57%). Respiratory system is the most common infection sites in the other four non Damp-heat syndrome groups. Infection sites in each group showed no statistical difference (P>0.05).㈡The correlational research between PNS Damp-heat syndrome and pro-inflammatory cytokines1.The comparison of pro-inflammatory cytokines expression levels between Damp-heat syndrome group and non Damp-heat syndromeThe serum hs-CRP (3.79±1.43ug/L) content was significantly higher in Damp-heat syndrome group than in non Damp-heat syndrome group (2.89±0.96 ug/L); urinary MCP-1 (32.55±5.90 pg/ml) content was also higher in Damp-heat syndrome group than in non Damp-heat syndrome group (29.12±3.95 pg/ml). By Statistical analysis, there were significant difference (P<0.05,P<0.05).The serum IL-6 (43.47±7.21pg/ml) level of Damp-heat syndrome was significantly higher than that of non Damp-heat syndrome group (35.77±5.27pg/ml); also the NF-κB activity (0.85±0.22) of Damp-heat syndrome group was higher than hat of non Damp-heat syndrome group (0.66±0.20), the statistical tests showed there were significant difference (P<0.01,P<0.01).2. The comparison of Damp-heat symptom scores and pro-inflammatory cytokines levels in treatment group and control group before treatmentBefore treatment, the Damp-heat symptom scores in treatment group was 4.50±0.80, in control group was 4.58±1.20, there were no significant difference (P> 0.05). In treatment group, the serum hs-CRP, IL-6 contents respectively were 3.69±1.42 mg/L,41.51±6.35pg/ml, urine MCP-1 content was 34.30±5.10pg/ml, PBMC NF-κB activity was 0.89±0.24. In control group, the serum hs-CRP, IL-6 expression levels respectively were 3.89±1.47mg/ L,45.44±7.64 pg/ml, urinary MCP-1 content was 30.81±6.25 pg/ml, PBMC NF-κB activity was 0.81±0.19. The statistical tests showed there were no difference between the two groups on these indicators (P>0.05)3. The comparison of Damp-heat symptom scores and pro-inflammatory cytokines levels in treatment group and control group after treatmentAfter treatment for 4 weeks, Damp-heat symptom score in treatment group was 2.45±0.99, in control group was 3.85±1.30, symptom scores in the two groups were significantly decreased compared with treatment before, by statistical test, there were significant differences (P<0.01, P<0.05). After treatment Damp-heat symptom score in treatment group was lower than in control group, by statistical test, there was significant differences (P<0.01).After treatment for 4 weeks, the serum hs-CRP level in treatment group and control group was respectively 2.63±0.67ug/L,3.32±0.89ug/L. Compared with treatment before, the serum hs-CRP level in the two groups were significantly decreased, by statistical test, there were statistically significant (P<0.01, P<0.05). The serum hs-CRP level in treatment group was significantly lower than in control group, by statistical test,there was statistically significant (P<0.01).After treatment NF-κB activity in treatment group and control group was respectively 0.54±0.19,0.68±0.23, NF-κB activity in the two groups were significantly decreased compared with treatment before (P<0.01, P<0.05). NF-κB activity in treatment group was also lower than in control group, by statistical test, there was statistically significant (P<0.05).After treatment the serum IL-6 level in treatment group was 23.36±3.64pg/ml, in control group was 34.68±6.79pg/ml, the serum IL-6 level in the two groups were significantly decreased compared with treatment before, the statistical tests showed there were significant difference (all P<0.01). The serum IL-6 in treatment group was significantly lower than in control group, by statistical test, there were significant differences (P<0.01).MCP-1 levels in treatment group and control group was respectively 22.17±3.6pg/ml,25.50±5.02pg/ml, there were significantly decreased compared with treatment before in the two groups, by statistical test, there were significant differences (all P<0.01). MCP-1 levels in treatment group was lower than in control group, the statistical tests showed there was significant difference (P<0.05).At the end of the treatment, the control group and the treatment group were respectively selected 10 cases to detect PBMC IL-6 mRNA expression, the result showed that IL-6 mRNA expression level (0.74±0.19) was significantly lower in treatment group than in control group (0.96±0.23), and there were statistically significant difference (P<0.05).4. The correlation analysis between Damp-heat factors and 24h urinary protein, NF-κB activity, serum IL-6 and urine MCP-1 content By correlation analysis of 40 damp-heat syndrome cases between damp-heat symptom scores and 24h urinary protein, damp-heat symptom scores and NF-κB activity, serum IL-6 and urine MCP-1 content before treatment, the results showed that damp-heat symptom scores was significantly positively correlated with 24h urinary protein (r=0.46,p<0.01), it also positively correlated with NF-κB activity, serum IL-6 and urine MCP-1 content (r Respectively=0.52,0.53,0.42, all p<0.01).Conclusion:1.By analysing 290 PNS cases from 2004.1 to 2010.1 in our hospital, the showed showed that Damp-heat syndrome is the principal syndrome of PNS, the occurrence in this study was 40.69%. 2. From the data of PNS cases'urinary protein, serum protein, lipids, incidence of infection, etc, the results showed that Damp-heat factor is an important reason leading to PNS patients'condition worsen. Damp-heat syndrome and infection are closely interrelated.3. Though comparing the levels of hs-CRP, IL-6, NF-κB, MCP-1 between Damp-heat syndrome group and non Damp-heat syndrome group, comparing changes of Damp-heat symptom scores and pro-inflammatory cytokines expression in Damp-heat syndrome treatment group and control group before and after treatment, analyzing the correlation between Damp-heat symptom scores and pro-inflammatory cytokines,the study showed that hs-CRP,IL-6,MCP-1-. NF-κB in Damp-heat syndrome cases abnormally increase, PNS Damp-heat syndrome is closely related to pro-inflammatory cytokines. |
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