Effects Of QiKui Granules On Oxidative Stress In Kidney Of Guinea Pigs With Insulin Resistance And Its Mechanism

ObjectiveThe effects of Qikui Granules on renal function and oxidative stress in insulin resistant guinea pigs were observed by molecular biology experiment,and whether the mechanism is related to the regulation of nrf2-keapl signaling pathway was explored.Methods1)The guinea pigs were randomly divided into 6 groups:control group,high-fat group,12H group,24H group,the Chinese medicine group and Melatonin group.After 6 weeks,under the same high-fat diet and light conditions,the traditional Chinese medicine group and MLT group were treated with Qikui granule and melatonin respectively for 4 weeks.2)The levels of fasting insulin,serum creatinine,blood urea nitrogen and C-reactive protein were detected by enzyme-linked immunosorbent assay after treatment to evaluate the difference of renal function and inflammatory state.3)ELISA was used to detect the changes of oxidative stress related indicators(NO,MDA,SOD)in kidney tissue after treatment.4)HE staining was used to observe the morphological changes of guinea pig kidney after treatment.5)The protein levels of Nrf2 and Keapl were detected by Western blot.Results1.After 10 weeks,the FBG,FINS and HOMA-IR of 24H group were significantly higher than those of 12H group,with statistical significance(P<0.05),indicating that the experimental insulin resistance model was successfully constructed,while the FBG,fins and HOMA-IR of the Chinese medicine group were significantly lower than those of 24H group,with statistical significance(P<0.05).2.Compared with 12H group,serum creatinine,blood urea nitrogen and C-reactive protein levels in 24H group increased,with statistical significance(P<0.05).Compared with 24H group,serum creatinine,blood urea nitrogen and C-reactive protein levels in the Chinese medicine group and MLT group increased,with statistical significance(P<0.05),C-reactive protein(CRP)and other indicators were significantly down regulated,with statistical significance(P<0.05).3.Compared with 12H group,the level of SOD in 24H group decreased significantly(P<0.05),the level of MDA and no increased significantly(P<0.05).Compared with 24H group,the level of SOD in the Chinese medicine group and MLT group increased significantly,the level of MDA and no decreased significantly(P<0.05).4.Histopathological method observed the changes of renal morphology in guinea pigs after treatment.In HE staining of kidney tissue,compared with the blank group,the renal lesions in 24H group were more serious and obvious renal damage occurred;compared with 24H group,after treatment with QiKui Granules and melatonin,the renal pathological changes were improved significantly.5.The effects of QiKui Granules on the expression level of Nrf2 and Keapl protein in guinea pig kidneyAfter treatment,Nrf2 protein expression in kidney of the Chinese medicine group and Melatonin group was significantly higher than that in 24H group,while that of Keapl was significantly lower than that in 24H group(P<0.05).Conclusions1.High fat diet and different light rhythm can lead to insulin resistance in guinea pigs.QiKui granules can improve insulin resistance.2.In 24H group,there were renal pathological changes and renal dysfunction,indicating that insulin resistance can lead to renal injury and renal dysfunction.3.QiKui Granules can significantly improve SCR,BUN and renal pathological changes,indicating that QiKui Granules has protective effects on kidney.4.QiKui Granules can reduce CRP in serum,which indicates that QiKui Granules has certain anti-inflammatory effects.5.Qikui granules can up regulate SOD in renal tissue and reduce NO and MDA in renal tissue,which indicates that QiKui granules has certain curative effect on anti oxidative stress.6.QiKui Granules may improve the oxidative stress response of guinea pigs by activating Nrf2/Keapl pathway,reduce the kidney injury caused by insulin resistance,and then play a protective role on the kidney.