The Research On Huatan Qushi Huoxue Recipe Intervention Nonalcoholic Steatohepatitis Rat Model Of ADPN/AKT/NF-KB Pathway

Objective : By observing Huatan Qushi Huoxue on biochemical indicators of nonalcoholic steatohepatitis in rat blood, liver pathological changes and ADPN/AKT/NF-KB signaling pathway key protein ADPN, Adipo R2,p-AKT(ser473), p-NF-KBp65(ser536) expression, and to explore the possible mechanism of prevention and treatment of NASH such party, provided the experimental basis for the prevention and treatment of NASH in medicine and drug development.Methods:Take SPF 72 healthy male SD rats, adaptive feeding one week, after which randomly divided into six groups:group(E) 12, according to the saline 1ml/ 100 g d-1 orally and infrastructure diet; the other five groups were free access to water, and high-fat diet(84% of the basal diet + 1% cholesterol + 5% + 10% egg yolk powder, lard) intraperitoneal injection of tetracycline modeling(1 times / week), the first injection quantity 10 mg / 100 g rat weight, after each injection volume of 7mg / 100 g rat weight. Model group(F) as before feeding; promoting blood phlegm dampness high dose group(group C) 5.04 g / 100 g · d-1, the middle dose group(group B) 2.52 / 100 g · d-1, the low-dose group(A group) 1.26 / 100 g · d-1 administered orally; polyene phosphatidylcholine capsule control group(group D) 0.0285 g / 100 g · d-1 administered orally. The first eight weeks end, after weighing all the rats weresacrificed, detect liver(ALT, AST, ALP), lipids(TC, TG), glucose(GLU) levels; observe liver weight, liver index, measured in liver homogenates FFA content; liver histopathological changes(HE staining); immunohistochemistry for ADPN, Adipo R2, p-AKT(ser473), p-NF-KBp65(ser536) protein localization and semi-quantitative determination.Results: 1.Compared with the control group(E group), model group(F) mice weight, liver weight, liver index, liver function(ALT, AST, ALP), lipids(TC, TG), glucose(GLU) and FFA content were significantly higher(P <0.01), and ADPN, Adipo R2, p-AKT(ser473) protein expression were significantly lower(P <0.01), significantly increased p-NF-KBp65(ser536) protein content(P <0.01) pathology(HE staining) showed moderate to severe steatosis. 2. Compared with the model group(F), each treatment group rat weight, liver weight, liver index, liver function(ALT, AST, ALP), lipids(TC, TG), glucose(GLU) and FFA content varying reduce the extent to which the high-dose group(group C), the most significant effect(P <0.01). And group C in regulated ADPN, Adipo R2, p-AKT protein expression and down on the p-NF-KBp65 protein, in addition to p-AKT expression and the control group index considerable effect(P> 0.05), the remainder are superior to all other drugs group(P <0.01). 3. Compared with the control group(group D), high-dose group(group C) were significantly better than in group D; middle dose group(group B) in mice reduced weight, liver weight, liver index, liver function(ALT, AST, ALP), lipids(TC, TG),glucose(GLU) and FFA content in terms of efficacy and D group fairly(P> 0.05), and slightly better than the low-dose group(A). In regulated ADPN, Adipo R2, p-AKT protein expression and reduced p-NF-KBp65 protein expression, the group B and group D considerable effect(P> 0.05), and better than the A group. 4. Correlation analysis showed that rat weight, liver weight, liver index, liver function(ALT, AST, ALP), lipids(TC, TG), glucose(GLU) and FFA content ADPN, Adipo R2, p-AKT negative correlation However, a positive correlation with the p-NF-KBp65 was. Dampness and phlegm promoting blood circulation to fight side effects NASH was positively correlated with their dose.Conclusion: 1. HQHR can effectively improve NASH rats liver function, lipids and other biochemical parameters regulating lipid metabolism and efficacy of high-dose group(group C) was significantly better than the control group(group D). 2. The existence and effect size HQHR dose effect relationship, the order of the effect that the high-dose group(group C)> dose group(group B)> low-dose group(A). 3. HQHR can upregulate ADPN 、 Adipo R2 、 p-AKT(ser473) expression in liver tissue,inhibit p-NF-KBp65(ser536) expression, thus effectively improve liver function, blood lipids and other biochemical markers, reverse NASH rat liver tissue steatosis extent, reduce inflammation of the liver, suggesting this may be one of the mechanisms for its prevention and treatment of NASH.