Protective Effect Of Jinlida On The Renal Of Insulin Resistance Rats Induced By A High-fat Diet

The metabolic syndrome is one of the serious diseases that threatens ourhuman,s healthy,it is also named insulin resistance syndrome.With the changesof human,s dietary structure and life style,the morbidity metabolic syndrome isincreasing year by year. Many factors of it such as renal disease arecomplications of diabetes mellitus,they both produced in the soil of “insulinresistance”. Hence enhance the research of chronic kidney disease,spathogenesis,and discover new effective medicine are very important.Jin lida is composed of ginseng, solomon’s seal, Radix Ophiopogonis,rhizoma atractylodis, kuh-seng, radices rehmanniae, Radix Polygoni MultifloriPreparata, Fructus Corni, eupatorium, Coptis chinensis, rhizomaanemarrhenae and Poria cocos. It can not only improve insulin resistance, butalso regulate blood lipid,therefore prevents and treats diabetes andcomplications from all aspects.The effect of jin lida on renal disease of insulin resistance rats isuncertain. The experiment first divided the SD rats into normal control groupand high-fat diet group, gave them standard diet and high-fat diet for6weeksto induce insulin resistance model. Use the hyperinsulinaemic-euglycaemicclamp to judge the model were builded successfully. And then further dividedthe rats into the normal control group(Con), high-fat fed insulin resistancegroup(HF), Jin lida of low/middle/high dose group(JLD-L/JLD-M/JLD-H),pioglitazone group(Pio), observed after administration of them8weeks bodyweight, fasting plasma insulin(FINS), glucose(FBG), glycosylated hemoglobin(HbA1c), blood lipid,GIR，HE staining, renal lipid, renal oxidative stress(MDA, SOD, CAT, GSH, GSH-PX)index, related gene and protein expressionto observe the protective effect of Jin lida on the renal of insulin resistance ratsinduced by a high-fat diet, provide theoretical basis for clinical application. Objective：To investigate the protective effect of Jin lida on the renal ofinsulin resistance rats induced by a high-fat diet, and the probable mechanismof it.Methods： Male Sprapue-Dawley (SD) rats (n=48) were randomlydivided into normal control group (Con)(n=12) and high-fat fed group (HF)(n=36)，gave them standard diet and high-fat diet for6weeks to induce insulinresistance model. Selective6rats in Each group and use thehyperinsulinaemic-euglycaemic clamp to judge the model were buildedsuccessfully.Then further divided the left36rats into six group(n=6):normalcontrol group(Con), high-fat fed insulin resistance group(HF), Jin lida oflow/middle/high dose group(JLD-L/JLD-M/JLD-H),pioglitazone group(Pio).After given drugs eigth weeks, observe body weight, fasting plasmainsulin(FINS), glucose(FBG), glycosylated hemoglobin(HbA1c), blood lipid，GIR，HE staining, renal lipid, renal oxidative stress (MDA, SOD, CAT, GSH,GSH-PX) index, related gene and protein expression.Results：1High-fat diet induced insulin resistance model：After fed6weeks,compared to the Con group, GIR decreased obviously but FBG、FINSincreased obviously in the HF group（P＜0.05）.The body weight of HF groupsignificantly increased compared to Con group（P＜0.05）, but the foodintake showed no significant change（P＞0.05）.2Effect of JLD on body weight and food intake:After the experimentfinished,the Body weight and food intake of HF group showed a significantincrease compared to Con group（P＜0.05）,and the body weight in JLD andpioglitazone group was decreased markedly than HF group（P＜0.05）,but thefood intake showed no significant change（P＞0.05）.3Effect of JLD on FINS, FBG and HbA1c: After the experimentfinished,compared to the Con group，the FINS、FBG and HbA1c of HF groupincreased obviously （P＜0.05）,and JLD and pioglitazone group bothdecreased significantly than HF group（P＜0.05）.In addition,the decreasing ofFBG and HbA1c was more obviously in the pioglitazone group. 4Effect of JLD on serum lipid profile: After the experiment finished,HFgroup exhibited dyslipidemia compared to Con group,FFA and TG in HFgroup were significantly higher than Con group（P＜0.05）,but TC showed nosignificant change（P＞0.05）. JLD group showed significantly reducing in theFFA, TG and TC levels than HF group（P＜0.05）. Pio group also significantlyreduced the FFA and TG level than HF group （P＜0.05）,while the TC wasfound no obvious change in the Pio group（P＞0.05）.5Effect of JLD on glucose infusion rete (GIR): After the experimentfinished,the euglycemic hyperinsulinemic clamp showed glucose uptake wasdecreased in HF group（P＜0.05）. However, this decrease was obviouslyreversed in JLD and pioglitazone group（P＜0.05）.In addition,the two druggroups showed no different in redecing insulin resistance.6Effect of JLD on HE staining of renal tissues: After the experimentfinished,HE staining showed that there were no obvious abnormalities in thekidneys of Con group.In the rats of HF groups,there were structural disorder inglomeruli and tubular,glomerular hypertrophy, mesangial areaexpansion,extracellular matrix increased.The abnormal changes werealleviated in JLD and pioglitazone group,although not normalized.7Effect of JLD on the content of renal lipid: After the experimentfinished,the content of FFA,TG in the HF group showed obviously increasecompared to the Con group,and JLD and pioglitazone group showedsignificantly decreased than HF group（P＜0.05）.8Effect of JLD on renal oxidative stress parameter and antioxidantmarkers: After the experiment finished,compared to the Con group,the contentof MDA was obviously higher and the activity or content ofSOD,CAT,GSH,GSH-Px was obviously lower in the HF group （P＜0.05）.Compared to the HF group,JLD and pioglitazone group couldameliorate the above markers except CAT.JLD group and pioglitazone groupshowed no difference.9Effect of JLD on the key enzyme and regulating factor of lipidsynthesis: After the experiment finished,compared to the Con group,the gene expression level of SREBP-1、ACC、FASN in the HF group increasedobviously（P＜0.05）,and JLD and pioglitazone group significantly decreasedthan the HF group（P＜0.05）.The protein expressions level of the key enzymeand regulating factor are consistent with the gene expressions.10Effect of JLD on the related enzyme and regulating factor ofoxidation/antioxidation: After the experiment finished,compared to the Congroup,the gene expression level of NOX2in the HF group was higher,andJLD and pioglitazone group were lowered than the HF group（P＜0.05）. TheNOX2protein expression was consistant with the gene expression.The geneexpression level of Nrf2was not found obviously change in the HF group （P＞0.05）,while the JLD and pioglitazone group showed significantly increasedthan the HF group（P＜0.05）. The total Nrf2protein expression level areconsistent with the gene expressions.But the expression of nuclear Nrf2protein in the HF group was lower compared to the Con group（P＜0.05）,andthe JLD-M,the JLD-H and the Pio group were increased significantly than theHF group（P＜0.05）.The HO-1protein expression was consistent with thenuclear Nrf2protein expression.Conclusion：High fat diet can lead to insulin resistance in rats.Jin lida hasprotective effect on the renal of insulin resistance rats induced by a high-fatdiet,probably because of reducing lipid synthesis and oxidative stress.