Investigation Of Cross - Sectional Area Of ​​nonalcoholic Fatty Liver And Adipokine Mechanism Of Qingre Qushu Huayu

Nonalcoholic fatty liver disease (NAFLD) is clinical syndrome of stress injured liver due to environment, genetics and metabolism, including simple nonalcoholic fatty liver, nonalcoholic steatohepatitis (NASH), cirrhosis and hepatic cancer. Nowadays, the morbility of NAFLD is increasing with the change both of live ways and dietary pattern. NAFLD treatment on traditional Chinese medicine (TCM) that has effective advantage both of whole and personality.while integrated western medicine and TCM could achieve complementary advantages. This study is to review NAFLD both treatment on western medicine and TCM and related mechanism on adipokines, discuss both on source of NAFLD liver fibrosis TCM theory and multidimensional differentiation therapy, systematic review and Meta-analysis on Sihe decoction based on NAFLD TCM treatment of clearing heat and expelling dampness and remove blood stasis. All these lead up to epidemiological investigation on NAFLD TCM diseases and syndromes and body constitutions,and discuss adipokines mechanism of NAFLD rat treatment on clearing heat and expelling dampness and remove blood stasis, so that improving the prevention and therapy on NAFLD.Objective:To study NAFLD TCM diseases and syndromes and body constitutions, and discuss adipokines mechanism of NAFLD rat treatment on clearing heat and expelling dampness and remove blood stasis.Methods:Reviewing NAFLD both treatment on western medicine and TCM and related mechanism on adipokines based on literature analysis.Discussing both on source of NAFLD liver fibrosis TCM theory and multidimensional differentiation therapy based on theory retrospect. Evaluating Sihe decoction based on NAFLD TCM treatment of clearing heat and expelling dampness and removing blood stasis through systematic review and Meta-analysis.Studying NAFLD TCM diseases and syndromes and body constitutions through epidemiological investigation.Discussing adipokines mechanism based on NAFLD rat model treatment on clearing heat and expelling dampness and removing blood stasis.Results:1、NAFLD treatment on TCM including inner therapy, external therapy and famous veteran teran doctors’experience, which strengthen syndromes differerntiation and integrated therapy. While NAFLD treatment on western medicine has not direct target drug so that emphasize prevention. Thus, integrated medicine could achieve complementary advantage to improve three prevention system on NAFLD.2、Liver fibrosis is key change to NAFLD. Pre-Qin, we could recognize the beginning cognition of liver fibrosis through abdominal diseases. Qin and Han Dynasties, the classic understanding of liver fibrosis including disease’s name, position, etiology pathogenesis, therapeutical principle, and so on. From the Wei Dynasty and Tang to Qing Dynasty, there were kinds of schools on liver fibrosis TCM standpoints. Therefore, TCM theory about liver fibrosis of NAFLD could be cleared primarily. NAFLD treatment on TCM could be seen from multidimensional effective therapies indeed, including etiology, pathogenesis, property, symptom, disease, constitution and syndrome differentiation, which could extend the TCM treatment system and educe the advantage of TCM effect.3、Evaluating Sihe decoction based on NAFLD TCM treatment of clearing heat and expelling dampness and removing blood stasis through systematic review and Meta-analysis. The methodology quality of all included randomized controlled trials (RCTs) belong to high risk bias. All RCTs did not report primary outcomes, but reported secondary outcomes. Systematic review and Meta-analysis on Chaihu Shugan Powder (CSP) that included10RCTs containing802NAFLD subjects, Meta-analysis results showed improvement on TC, LDL, HOMA-IR, ALT, AST, GGT, TBiL, ALP, HA, LN, PCIII, PCIV, liver B-type ultrasonography score, total effective power,flank flatulency improvement rate,abdominal distention improvement rate, after CSP treatment compared to controlled group. Systematic review and Meta-analysis on Yinchenhao Decoction (YD)that included14RCTs containing1214NAFLD subjects, Meta-analysis results showed improvement on ALT, AST, GGT TG, TC, LDL, liver B-type ultrasonography score, total effective power, syndrome score improvement rate, syndrome effective power, after YD treatment compared to controlled group. Systematic review and Meta-analysis on glycyrrhiza uralensis active priciple(GAP)that included28RCTs containing2260NAFLD subjects,Meta-analysis results showed improvement on AST,ALT,GGT,TBiL,TBA,TG,TC,FBG,2hPG, HOMA-IR,CRP,TNF-a improvement rate, liver B-type ultrasonography score.total effective power, symptom improvement rate, after GAP treatment compared to controlled group.4、Total98NAFLD subjects included to the epidemiology investigation and statistical analysis. Mean age was (60.9±14.7) years, mean disease course was (2.7±3.0) years, mean body mass index (BMI) was (24.5±3.5) Kg/m2. Liver B-type ultrasonography classification79.6%belong to mild level,14.3%to moderation, and6.1%to severity of NAFLD. NAFLD complicated with hypertension was43.9%, cardiovascular disease was22.4%, diabetes mellitus was19.4%, hyperlipoidemia was18.4%,and cerebrovascular disease was17.3%. Liver function, blood fat, blood clotting and inflammation indexes of NAFLD were normal roughly. NAFLD body constitutions of phlegm-damp was34.7%, heat-damp16.3%, blood stasis16.3%, qi stagnation10.2%, yang asthenia6.1%, harmony6.1%, qi deficiency3.1%heat-damp combined blood stasis3.1%, phlegm-damp combined qi stagnation1.0%, qi deficiency combined blood stasis1.0%, qi deficiency combined yin asthenia1.0%, yin asthenia1.0%. NAFLD syndrome differentiation belong to retention of phlegmatic dampness was31.6%, stagnation of damp-heat23.5%, phlegm accumulating with stagnant blood20.4%, obstructing of turbid damp13.3%, stagnation of qi due to depression of the liver8.2%, hepatic stagnation causing splenic deficiency3.1%.5、(1) NAFLD rat model weight were not significant difference between groups in every week course (P>0.05). At9week2-3rats of every groups were selected randomly to observe and compare tongue demonstration,which showed normal rats group tongue was rosy,NAFLD model rats group tongue was red and ecchymosis and fat,low dose TCM rats group tongue was red and ecchymosis.middle dose TCM rats group tongue was dark red, high dose TCM rats group tongue was dim. Liver humid weight index was significant difference about low dose TCM group, middle dose TCM group, high dose TCM group, model group that each compared to normal group (P<0.01). Liver humid weight index was not significant difference between low dose TCM group middle dose TCM group,high dose TCM group and model group(P>0.05). Perirenal and epididymis fat weight was not significant difference between every group (P>0.05), as well as body fat ratio and Lee’s index (P>0.05). Macroscopic observation about hepatic appearance showed that model group hepatic morphology was significant augmentation, liver was pale and weight was significant augmentation, envelope was tension and surface was rough and butyrous, marginal was muticate and round, texture was soft, liver was significant adhesion with peri-architecture, Perirenal and epididymis was lots of fat tissue. Sihe decoction treatment groups could ameliorate hepatic morphology significantly, while middle dose TCM group was best effect. Hematoxylin and eosin stain (HE) showed that model group liver tissue was adipose degeneration and accumulation severely, hepatic cord architecture was disturbance, hepatic cells ballooning degeneration and swollen deformation, kytoplasrn was lots of lipid droplet and nucleus was dyssymmetry, lots of inflammatory cell infiltration, lobula displayed necrotic tissue. Sihe decoction treatment groups could amelorate HE pathology significantly, while high dose TCM group was best effect. Masson stain showed that model group perisinus and portal area was fibrosis, fibrous tissue proliferated significantly, inflammatory cell infiltrated, false lobule was not formation. Sihe decoction treatment groups could ameliorate Masson pathology significantly, while high dose TCM group was best effect. Oil red O stain showed that model group liver tissue was massive red area, cytoplasm was lots of lipid droplet, lobula lipid droplet cells proportionalit with other cells was70-90%. Sihe decoction treatment groups could ameliorate oil red O pathology significantly, while high dose TCM group was best effect.(2) Sihe decoction based on clearing heat and expelling dampness and removing blood stasis treated NAFLD rats showed that ALT and AST between every group were not significant difference (P>0.05). HDL was significant difference between low dose TCM group and normal group after Sihe decoction treatmen(P<0.05),as well as LDL between middle dose TCM group, high dose TCM group and normal group (P<0.05) TC and TG were not significant difference between every group; P>0.05), as well as FBG, ISI, FINS, IRI, AFP and C-P (P>0.05).(3) AdipoR2expression was significant lower in model group, middle dose TCM group and low dose TCM group compared to normal group (P<0.05). AdipoR2expression was significant higher in high dose TCM group compared to model group (P<0.05). AdipoR2expression was significant higher in high dose TCM group compared to low dose TCM group (P<0.01). AdipoR2expression was significant higher in high dose TCM group compared to middle dose TCM group (p<0.05). AdipoR2/β-actin ratio was significant lower in model group, middle dose TCM group and low dose TCM group compared to normal group(P<0.05). AdipoR22/(3-actin ratio was significant higher in high dose TCM group compared to model group (P<0.05). AdipoR22/β-actin ratio was significant higher in high dose TCM group compared to low dose TCM group (P<0.01). AdipoR22/β-actin ratio was significant higher in high dose TCM group compared to middle dose TCM group(P<0.05). AdipoR1expression was significant lower in model group, middle dose TCM group and low dose TCM group compared to normal group (P<0.005). AdipoR1expression was significant higher in middle dose TCM group compared to model group (P<0.05). AdipoR1/β-actin ratio was significant lower in model group, middle dose TCM group and low dose TCM group compared to normal group (P<0.05). AdipoRl/β-actin ratio was significant higher in middle dose TCM group compared to model group (P<0.05).(4)Visfatin concentration was significant higher in middle dose TCM group Jow dose TCM group and high dose TCM group compared to normal group (P<0.05). Visfatin concentration was significant higher in middle dose TCM group compared to model group(P<0.05). APN was significant higher in model group.middle dose TCM group, low dose TCM group and high dose TCM group compared to normal group(P<0.05). APN concentration was significant lower in low dose TCM group compared to model group (P<0.05). APN concentration was significant higher in high dose TCM group compared to model group(P<0.01). APN concentration was significant higher in high dose TCM group and middle dose TCM group compared to low dose TCM group (P<0.01). APN concentration was significant higher in high dose TCM group compared to middle dose TCM group (P<0.05). LEP concentration was significant higher in middle dose TCM group, model group and high dose TCM group compared to normal group (P<0.01). LEP concentration was significant lower in low dose TCM group compared to model group (P<0.05). LEP concentration was significant higher in high dose TCM group and middle dose TCM group compared to low dose TCM group (P<0.05). LEP concentration was significant higher in high dose TCM group compared to middle dose TCM group(P<0.05). Resistin concentration was significant higher in middle dose TCM group, low dose TCM group and high dose TCM group compared to normal group (P<0.01). Resistin concentration was significant higher in middle dose TCM group and high dose TCM group compared to model group (P<0.05). Resistin concentration was significant higher in high dose TCM group compared to low dose TCM group (P<0.05). Resistin concentration was significant higher in high dose TCM group compared to middle dose TCM group(P<0.05).TNF-a concentration was significant higher in model group compared to normal group (P<0.01). TNF-a concentration was significant lower in middle dose TCM group, low dose TCM group and high dose TCM group compared to model group (P<0.01). IL-6concentration was significant higher in middle dose TCM group, low dose TCM group, model group and high dose TCM group compared to normal group (P<0.01). IL-6concentration was significant lower in middle dose TCM group, low dose TCM group and high dose TCM group compared to model group (P<0.01). PCIII concentration was significant higher in middle dose TCM group Jow dose TCM group, model group and high dose TCM group compared to normal group (P<0.01). PCIII concentration was significant lower in low dose TCM group compared to model group (P<0.01). PCIII concentration was significant higher in high dose TCM group compared to model group(P<0.01). PCIII concentration was significant higher in high dose TCM group and middle dose TCM group compared to low dose TCM group (P<0.01). PClli concentration was significant higher in high dose TCM group compared to middle dose TCM group (P<0.01). CIV concentration was significant higher in middle dose TCM group, low dose TCM group, model group and high dose TCM group compared to normal group (P<0.01). CIV concentration was significant higher in high dose TCM group compared to middle dose TCM group, low dose TCM group and model group (P<0.05). HA concentration was significant higher in middle dose TCM group, low dose TCM group, model group and high dose TCM group compared to normal group (P<0.01). HA concentration was significant higher in high dose TCM group compared to middle dose TCM group, low dose TCM group and model group (P<0.01). LN concentration was significant higher in high dose TCM group compared to middle dose TCM group, low dose TCM group, normal group and model group (p<0.01).Conclusions: 1、Basing on comprehensive methods including review,theory discussion,systematic review and Meta-analysis,tutor’s clinical experience gnosis,et al.,presuming NAFLD effective prevention and treatment should integrate TCM, western medicine activeness of personality and improvement of popular healthy science construction. The close relationship between causes of NAFLD and metabolic syndromes network kinds of adipokines activity, and reveal adipokines mechanism of NAFLD gradually. Liver fibrosis is important pathology of NAFLD. The source of NAFLD liver fibrosis TCM theory contains disease’s name,position,etiology,pathogenesis,therapeutical principle,formulae,schools,and so on,which would promote the guidance on NAFLD liver fibrosis TCM treatment. Thus, NAFLD multidimensional differentiation therapy based on theory retrospect including etiology, pathogenesis, property, symptom, disease, constitution and syndrome differentiation, which could extend the TCM treatment system and educe the advantage of TCM effect. Evaluating Sihe decoction based on NAFLD TCM treatment of clearing heat and expelling dampness and removing blood stasis through systematic review and Meta-analysis, results showed CSP, YD and GAP were both effective and safety, but the methodology quality of all included randomized controlled trials (RCTs) belong to high risk bias, so that rigorously RCT should be conducted to support NAFLD treatment on CSP, YD and GAP.2、Total98NAFLD subjects included to the epidemiology investigation and statistical analysis on TCM diseases and syndromes and body constitutions. Liver function, blood fat, blood clotting and inflammation indexes, et al., of most of NAFLD subjects were normal, indicating there are lacking specificity index on NAFLD comprehensive evaluation. Synthesizing results indicated body constitutons of phlegm-damp, heat-damp.blood stasis and combination are the most common to NAFLD,as well as syndromes of retention of phlegmatic dampness, stagnation of damp-heat, phlegm accumulating with stagnant blood, obstructing of turbid damp. Acrid could permeate into qi and blood that activate qi and disperse blood stasis.3、NAFLD rats model treatment on Sihe decoction based on clearing heat and expelling dampness and removing blood stasis indicated NAFLD model was successful copy,liver humid weight index,Lee’s index were significant increase.Sihe decoction could improve liver pathology morphology, while middle dose TCM group was best effect. HDL and LDL were the primary targets of Sihe decoction to treat NAFLD, while there were not change on ALT, AST, TC, TG, FBG, IRI, ISI, AFP and C-P. Both AdipoR2mRNA and AdipoR1mRNA expression in NAFLD liver tissue, Sihe decoction could improve NAFLD through enhancing AdipoR2mRNA and AdipoR1mRNA expression, while high dose TCM group was best effect on AdipoR2mRNA expression and middle dose TCM group was best effect on AdipoR1mRNA expression. NAFLD could induce liver tissue expression of APN, LEP, TNF-a and IL-6, Sihe decoction could not only down regulate TNF-a and IL-6expression, but up regulate Visfatin,APN,LEP and Resistin expression,while high dose TCM group was best effect on up regulation of APN, LEP and Resistin, middle dose TCM group was best on up regulation of Visfatin expression, low dose TCM group was best effect on down regulation of APN and LEP espression.Therefore, Sihe decoction could improve NAFLD by network and mulit-target regulation on adipokines.