Studies On The Effects And Mechanism Of Berbamine Hydrochloride In Preventing Type 2 Diabetic Nephropathy

Type 2 Diabetes Mellitus(T2DM)is a metabolic syndrome caused by genetic variation,immune dysfunction and environmental factors.Its basic characteristic is persistent chronic hyperglycemia.The clinical symptoms are "three more and one less symptoms" of drink a lot,eat a lot,urinate a lot,and weight loss.Type 2 diabetic nephropathy is more common and severe in chronic complications of type 2 diabetes mellitus.In this paper,a mouse model of type 2 diabetic nephropathy was successfully replicated by intragastric administration of Kunming mice with high-fat,high-fat fat emulsion for 1 month and intraperitoneal injection of streptozotocin(STZ).Then through the preliminary experiment confirmed that berbamine hydrochloride has certain antidiabetic effect and can prevent diabetic nephropathy,its anti-diabetic nephropathy effect is stronger than the same molar concentration of berberine hydrochloride.Then the preventing effect of berbamine hydrochloride on diabetic nephropathy and its mechanism were studied through further pharmacodynamic experiments and mechanism research.The mice were divided into normal control group,model control group,low,medium and high doses of berbamine hydrochloride(70mg/kg,140mg/kg,280mg/kg),rosiglitazone(70mg/kg,positive drug),and the corresponding drugs were administered to each group for 45 days by intragastric administration.The physiological and biochemical indexes such as body weight,fasting blood glucose,insulin,high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),blood urea nitrogen(BUN),serum creatinine(Scr),total 24 h urine protein and 24 h urine volume were measured.The kidney and pancreas of every group were taken to make paraffin sections and to do HE staining,and the changes of the cells in the tissues were studied.The expression of TNF-? and TGF-? in kidney tissue was studied by western blot to reveal the mechanism of berberine hydrochloride in preventing diabetic nephropathy.(1)Researches on the physiological and biochemical indexes showed that low,medium and high doses(70 mg/kg,140 mg/kg and 280 mg/kg)of berbamine hydrochloride can significantly alleviate the fasting blood glucose level of mice with type II diabetic nephropathy,and can significantly reduce TG levels,increase HDL-C levels,and the functions are dose-dependent.It was illustrated that berbamine hydrochloride has certain antidiabetic effects,and the antidiabetic effect of high dose group was obviously better than that of the positive control drug,rosiglitazone(70mg/kg).(2)Berbamine hydrochloride at 70mg/kg,140mg/kg,280mg/kg could significantly reduce serum Scratinine(Scr),blood urea nitrogen(BUN)and total urine protein,which is dose-dependent.The antidiabetic nephropathy effect of medium and high dose group of berylamine hydrochloride was better than that of positive control drug rosiglitazone.The results showed that berbamine hydrochloride had a good effect for the prevention of diabetic nephropathy.(3)By studying the paraffin sections of the pancreas of every group it could be found that low,medium and high dose of berbamine hydrochloride have the abilities of protecting islet ? cells,and the abilities are dose-dependent.By studying the paraffin sections of the kidneys of every group it could be found that low,medium and high doses of berbamine hydrochloride have the ability to protect kidney glomeruli and renal tubules,and the abilities are dose-dependent.The protective effect of berbamine hydrochloride on renal tissue was stronger than that of rosiglitazone.(3)Studies on the mechanism of berbamine hydrochloride for the prevention of type 2 diabetic nephropathy showed that medium and high doses of berbamine hydrochloride(140mg/kg,280mg/kg)can significantly reduce the expression of TNF-? and TGF-? in the kidney of type 2 diabetic nephropathy mice,and the reducting effect of berbamine hydrochloride at medium and high doses(140mg/kg and 280 mg/kg)is stronger than that of rosiglitazone administration group(70mg/kg,positive control).It could be speculated that berbamine hydrochloride may play a role in alleviating renal diseases partly by preventing the inflammation of renal tissue and mainly by inhibiting extracellular matrix(ECM)secretion and preventing the fibrosis of renal cells.