Mechanism And Protective Effect Of Chaihushugan Powder On Insulin Resistance Of Nonalcoholic Fatty Liver Model In Rat

Objeceive: To establish nonalcoholic fatty liver disease (NAFLD) and insulin resistancemodel by feeding rats with high fat and sugar emulsion with Chaihushugan powder tointervene, evaluate the effect of Chaihushugan powder on insulin resistance ofnon-alcoholic fatty liver disease rats and its possible mechanism, and supply furtherscientific evidenee for chaihushugan powder clinic treatment to NAFLD.Methods: The rats were randomly divided into: normal、model、Dongbaogantai（0.09gmethionine/kg）、Chaihushugan powder high、medium、low doses(12.6、6.3、3.15g medicinalherbs/kg). Except the normal group，the rats in other groups were administered by i.g highfat and sugar emulsion (10ml/kg) besides basic diet to induce NAFLD. After treatment for8weeks，all the rats with3%sodium pentobarbital (by dose1ml/kg) anesthesia, abdominalaortic blood and timely removal of the liver. Rat liver morphology and visual observationof each group weighed wet weight changes in a timely manner. Observed the pathologicallesions in rat liver tissue by naked eye and promptly weighed the liver wet weight, gradingthe liver cells steatosis degree by light microscope. The contents of TC, TG, HDL-C, FFA,ALT，AST，fasting plasma glucose(FPG), fasting insulin(FINS) in the serum，as well asTC，TG，SOD，MDA，T-GSH in the hepatic homogenate were detected by automaticbiochemical analyzer, and homeostasis model assessment was applied to assess the status ofinsulin resistance (IR)，insulin sensitive index (ISI), insulin secretion index (HOMA–IS).The expression levels of adiponectin and leptin mRNA in liver tissue were analyzed byreverse transcription polymerase chain reaction (RT-PCR).Results: Compared with normal group, model group rats serum TC, TG, LDL-C, FFA, FBG,FINS, IRI, AST and ALT were significantly increased (P <0.01), serum HDL-C, the ISI, HOMA-IS were significantly reduced (P <0.01), liver index and liver TC, TG and MDAlevel were significantly increased (P <0.01), liver SOD activity decreased obviously,Adiponectin mRNA expression significantly reduced (P <0.01), Leptin mRNA expressionquantity increased significantly (P <0.01);Liver pathological display model group ratsdisorganized hepatocyte and hepatic lobule boundary is not clear, hepatic sinus disappeared,liver cell volume are increased, the swelling shaped, diffuse fatty degeneration.Comparedwith the model group，the serum TC，TG，HDL-C,ALT,AST,MDA,FFA,FPG, FINS levelsand the liver levels of TC and TG in Chaihushugan powder high、medium、low doses groupwere significantly decreased (P<0.01or P<0.05) and the levels of ISI, HOMA-IS inChaihushugan powder high、medium、low doses group were significantly increased(P<0.01or P<0.05);the expression of leptin mRNA in the hepatic tissue in Chaihushugan powderhigh、medium、low doses group were significantly decreased (P＜0.01), and the expressionof adiponectin mRNA in the hepatic tissue in Chaihushugan powder high、medium、lowdoses group were significantly increased(P＜0.01); to the decreasing of liver index、theincreasing of SOD and T-GSH in Chaihushugan powder high、medium、low doses grouphave no significant difference; liver pathological section showed the hepatocyte adiposedegeneration、water samples degeneration、cell infiltration in Chaihushugan powder groupswere significantly lighter than model group.Conclusion: The subject was successfully replicated in line with human characteristics ofNAFLD and insulin resistance rat model by fed high fat and sugar emulsion eight weeks, issimilar to modern humans NASH metabolic changes caused by diet, having the samepathogenesis, is the ideal model of NASH.Chaihushugan powder can effectively reduce the hepatic steatosis in NAFLD rats, reduceserum lipid levels, liver lipid levels, and liver lipid peroxidation, improve insulin sensitivityand protect the liver from damage, can significant up-regulating of expression ofAdiponectin mRNA and down-regulating expression of leptin mRNA in rat liver tissue.Itspossible mechanism for:(1)by increasing peripheral fatty acid oxidation ability, reducingthe absorption of exogenous lipids, reducing the generation of endogenous lipid transportand enhancing hepatic lipid accumulation to reduce the lipid body;(2)by eliminating a large number of liver the ROS and free radicals to enhance the ability of the liver againstoxidative stress;(3)by stabilizing liver cell membrane repair to damage liver cells, reducingliver cell degeneration and necrosis, to protect and promote regeneration of livercells;(4)by lowering blood glucose and insulin levels and enhancing insulin sensitivity toinsulin resistance;(5)by upregulating the expression of hepatic adiponectin to enhance thebinding of insulin to cell membrane receptors significantly increased hepatic insulinsensitivity sensibility, enhancing hepatic fatty acid β-oxidation, reducing lipidaccumulation in the liver and hepatic gluconeogenesis and hepatic glucose output toimprove insulin resistance, to promote liver fat metabolism in liver leptin expression;(6)bydown regulating liver tissue sensitivity to insulin, and enhancing the periphery of fatty acidoxidation capacity and inhibiting of peripheral lipogenesis to reduce inhibiting liver fataccumulation and suppressing inflammation.