Effects And Differences Of Huang-Lian-Jie-Du Decoction And Berberine On Kidney During Treatment Of Type 2 Diabetic Rats

Objective Diabetic kidney disease(DKD)as one of the most common and serious microvascular complications of diabetes,its incidence is going to increase every year.This complication not only affects the quality of patients,life,gives a heavy load to social and family,but also has threatened the lives of patients.Therefore,how to effectively delay its development is of great importance.Huang-lian-Jie-du Decoction and berberine have been found they can reduce blood glucose in recent years.Berberine has been confirmed it can delay the progression of DKD.But there are few studies about Huang-lian-Jie-du Decoction on the kidney,and compared with berberine,there are more active ingredients,interactions between the components and less adverse reactions of Huang-lian-Jie-du Decoction.In this study,aims to observe the effect of two drugs on kidney and whether there is a difference in efficacy between them,we selected spontaneously type 2 diabetic ZDF rats as our study subjects,and they were treated with Huang-lian-Jie-du decoction and berberine respectively when induced to the stage of diabetes.Methods 30 male Specific pathogen Free ZDF rats were fed with Purina#5008 and randomly divided into 3 groups(10 for each): Model group,Huanglian group and Berberine group when they were induced to the stage of diabetes.Another 5 normal ZL rats were used as normal control.The Huanglian group and Berberine group was treated with Huang-lian-Jie-du decoction and berberine at dose of 0.075g/d and 100mg/kg/d respectively,and the Model group and Normal group were fed the equal amount of distilled water.Drug intervention for 6 weeks as the experimental endpoint.During the experiment,blood glucose and body weight were recorded in different periods,24-hour urine was taken for 24 h UTP.Blood samples were taken for blood lipid,kidney function.Fasting plasma insulin were measured by ELISA,and HOMA-IR index was calculated to evaluate insulin resistance.Urine samples were taken for NAG,GAL and β2-MG.Renal tissues were kept,and the HE staining and ultrastructure of glomeruli and proximal convoluted tubules in kidney tissue of rats were observed.Results 1.General indicators: Fasting blood glucose and body weight of ZDF rats in the model group gradually increased with progression of disease.After 6 weeks of drug intervention,fasting blood glucose(P<0.01),body weight(P<0.01),fasting insulin levels(P <0.01),insulin resistance(P<0.01),and blood lipids including TC(P <0.01),TG(P <0.01),LDL-C(P <0.05)and HDL-C(P <0.01)were found in model group significantly higher than that of normal group.Compared with the model group,fasting blood glucose levels(P <0.01)and insulin resistance(P<0.01),TC(P <0.05)and TG(P <0.05)in the Huanglian group and Berberine group decreased significantly(P <0.01),weight,LDL-C and HDL-C decreased slightly(P >0.05).Fasting insulin levels in the berberine group decreased significantly than model group(P <0.01),Huanglian group decreased slightly(P > 0.05).2.Kidney structure test indicators: 1)24-hour urinary protein quantification: With the progression of the disease,24 h UTP was gradually increased in the model group.After 6 weeks of drug intervention,24 h UTP in the model group was significantly higher than that in the normal group(P <0.01).Huanglian group and Berberine group was significantly lower than the model group about 24 h UTP(P <0.01).2)Tubular biomarkers: After 6 weeks of drug intervention,the levels of NAG,GAL in the model group were significantly higher than those in the normal group(P <0.01).GAL in the Huanglian group and berberine group were significantly lower than the model group(P <0.05).The decline in Huanglian group(P <0.05)about NAG was more obvious than that in the berberine group(P >0.05).There was no significant difference in urine β2-MG between the four groups(P >0.05).3.Renal function: After 6 weeks of drug intervention,the urea nitrogen(BUN)in the model group was significantly higher than that in the normal group(P <0.01),while the serum creatinine(Scr)was significantly decreased(P <0.01).Compared with the model group,the levels of BUN in Huanglian group and berberine group decreased slightly(P >0.05).There was no significant difference in Scr(P >0.05).4.Pathological structure of kidney tissue: 1)HE staining: The glomerular,renal interstitial and renal tubular structures in the normal group were normal.In the model group,the glomerular structure of rats was destroyed,glomerular sclerosis occurred,renal tubular epithelial cells became necrotic,and the lumen became smaller and atrophy.The glomerular and renal interstitial structures in the Huanglian and berberine groups were acceptable.No glomerular sclerosis were seen.There was no necrosis in the renal tubular epithelial cells,although some lumens became smaller.2)Observing the ultrastructure of the kidney under electron microscope: There was no obvious abnormality in the structure and morphology of glomeruli and renal tubules in the Normal group.The Model group had thickened segmental glomerular filtration membrane,unclear structure,focal fusion and destruction of the foot process.The proximal tubular epithelial cells were vacuolated and the structure of the labyrinth was unclear.There were more lysosome particles in the cells,and some of the tubular cells had nuclei shrinking and showing apoptotic changes.In the Huanglian group and Berberine group,the structure of filtration membrane and proximal curved tubule was also significantly improved compared with the Model group.Conclusion 1.Huang-lian-Jie-du decoction and berberine can reduce blood glucose,body weight,blood lipid,insulin levels and insulin resistance of ZDF rats,and improve the general condition of rats.2.Huang-lian-Jie-du decoction and berberine can reduce the 24-hour urinary protein,urine NAG,GAL and blood urea nitrogen levels of ZDF rats,and improve the pathological structure of glomeruli and renal tubules,which has a positive effect on the kidney and prevents the development of DKD.3.Huang-lian-Jie-du decoction like berberine can also have a protective effect on the kidney,and can prevent the development of DKD.