Exploring The Mechanism Of The Chinese Medicine Xuezhikang Based On PPARα/PGC-1α Signaling Pathway To Intervene In Obesity Hypertension Combined With Metabolism-associated Fatty Liver

Objective of the study:Obese hypertension combined with metabolic fatty liver is becoming more and more common,and there is no targeted and effective drug,while Xuezhikang is a safe and effective natural Chinese medicine to lower lipid.By evaluating the lesion degree of obese spontaneously hypertensive rats complicated with metabolic associated fatty liver disease induced by high fat feeding,the efficacy of Xuezhikang on improving obese spontaneously hypertensive rats complicated with metabolic associated fatty liver disease was investigated.And through the study of pathological changes in rat liver,PPARα/PGC1-αsignaling pathway related protein expression.To investigate the mechanism of Xuezhikang in improving metabolic associated fatty liver disease in obese spontaneously hypertensive rats.METHODS:A model of spontaneously hypertensive rats combined with metabolic fatty liver was obtained by high-fat feeding.Twenty-four 6-week-old male spontaneously hypertensive rats(SHR)were randomly divided into a high-fat diet group(n=12)and a normal diet group(n=12).The standard diet group was given ordinary diet,and the high-fat diet group was given high-fat diet,and after 1 week of adaptation feeding,the normal diet group and the high-fat diet group were randomly and equally divided into 6 in the Xuezhikang treatment group(300 mg/kg/d by gavage)and 6 in the model control group(The same volume of saline,gavage);4 groups in total.Both treatment and control groups were intervened continuously for 16 weeks.At the end of the experiment period(week 16),the rats were killed with an overdose of sodium pentobarbital(250mg/kg,intraperitoneal injection).Blood and liver specimens were collected and tested for the following indicators:(1)The levels of body weight and blood pressure changes in rats were monitored during the experimental cycle,and statistics were collected.To investigate the effect of Xuezhikang on the body weight and blood pressure of obese spontaneously hypertensive rats.(2)Enzyme-linked immunosorbent assay(Elisa)to detect serum and liver free fatty acid(FFA)and triglyceride(TG)levels in each group of rats(3)The pathological changes of liver were observed by hematoxylin-eosin(HE)and oil red O(ORO)staining,and the morphology and degeneration of liver fat were evaluated.(4)Western blot was used to detect the protein expression levels of PPARα,PGC-1A-α and CPT1-A in SHR liver tissues of each group after Xuezhikang treatment.To investigate whether Xuezhikang can up-regulate the expression of the above proteins.Results of the study:(1)Xuezhikang can reduce the blood pressure,especially the systolic blood pressure(DBP)of obese hypertensive rats.And lose weight.(2)The levels of triglycerides(TG)and free fatty acids(FFA)in the liver of high-fat-fed spontaneously hypertensive rats were significantly increased,and the TG and FFA in the liver of the HFD-X group were significantly reduced by the intervention of Xuezhikang compared with the HFD group.(3)Xuezhikang can reduce fat accumulation in the liver of obese hypertensive rats and improve hepatic cell steatosis.(4)Xuezhikang could up-regulate the protein expression of PPARα,PGC-1Aaand CPT1-a.Conclusion:Xuezhikang may reduce the blood pressure and body weight of spontaneously hypertensitive rats fed with high fat through the PPARα/PGC-1α signaling pathway,and improve the problems of intrahepatic fat accumulation and steatosis of hepatocytes caused by metabolic associated fatty liver disease.