| Diabetic nephropathy(DN)is one of the most frequent and severe chronic complications of diabetes mellitus(DM).DN is also known as diabetic glomerular sclerosis,with many patients pro-recognized as the leading gressing to end-stage renal disease(ESRD)and requiring dialysis or transplantation.At present,despite a variety of treatment options including renin-angiotensin aldosterone system(RAAS)blockade with ACEI/ARB,the renal funcation failure due to DN still remains high.Qi Kwai Granules is an effective prescription for the treatment of DN in Jiangsu Province Hospital of TCM,Dr.Yu Jiangyi founded.However,the therapeutic mechanisms of Qi Kwai Granules are not clear.Terefore,we examined whether Qi Kwai Granules would enhance the efficacy in slowing the progression of DN and explored the treatment mechanisms of Qi Kwai Granules on renal injury of DN in our studies.This subject aims to provide more evidence for subsequent researches and clinical application of Qi Kwai Granules and a new perspective for the development of new drugs and novel clinical treatment of DN.Part 1,the diuretic effects of Qi Kwai Granules on normal rats and water loaded rats are studied in this part.We recorded the urine volumes per hour within 6 hours and detected pH values and the concentrations of Na+,K+,Cl-in the urines of the normal rats to research the diuretic effect of Qi Kwai Granules on normall rats.In addition,the diuretic action of Qi Kwai Granules on water loaded rats was studied by comparison of urine volumes in 7h in each group of water loaded rats.Results:urine of Qi Kwai Granules in each dose group within 6h were increased,the urine volumes of Qi Kwai Granules of high dose group in 3h and 4h were statistically different compared with the blank group(p<0.05,p<0.01).The concentrations of Na+,C1-of Qi Kwai Granules high,middle dose groups were increased and the concentrations of K+of Qi Kwai Granules high dose group was decreased,there were significant distinguishment compared with the control group(P<0.01,P<0.05).The urine volumes of Qi Kwai Granules in each dose during 1-3h,3-5h,5-7h and the average urine volumes in 7 hours were raised,there were significant difference compared with the control group(P<0.01,P<0.05).Qi Kwai Granules have good diuretic effect.Qi Kwai Granules can increase the excretion of urine and its possible mechanism maybe relate to its stimulative effect of the excretion of Na+,Cl-and prevention of the excretion rate of K+.Part 2,the anti-inflammatory effects of Qi Kwai Granules were demonstrated by two anti-inflammatory experiments:the inflammatory response which was induced by xylene in mice,and the rats paw swelling reaction of carrageenin.OD value of inflammatory mice skin tissue was measured to determine the anti-inflammatory effect of Qi Kwai Granules;prostaglandin E2(PGE2)content of the rat foot swelling induced by carrageenin were determinated by ultraviolet spectrophotometer to observe the inhibitory effect of Qi Kwai Granules.Results:In the anti-inflammatory experiment induced by xylene in mice,xylene induced mice skin capillary permeability expanded and the OD value of Qi Kwai Granules of high、medium、low dose groups were decreased significantly compared with the control group(P<0.01).Qi Kwai Granules have good effects against inflammation induced by xylene.Moreover,Qi Kwai Granules have the anti-inflammatory effect for the paw swelling of rats induced by Carrageenan.6h swelling rate of high dose group and 2-6h swelling rate of Qi Kwai Granules were significantly lower,which have significant difference compared with the control group(P<0.01,P<0.05).Qi Kwai Granules of medium group has good inhibitional effect of foot swelling compared with the control group(P<0.01).Inhibition rates of Qi Kwai Granules of medium group in 1-6 hours respectively were 27.54%,31.95%,28.07%,33.64%,20.93%,21.62%.The content of PGE2 of Qi Kwai Granules of high,medium,low dose groups were demonstrably decreased,which have evident difference compared with the control group(P<0.01).Qi Kwai Granules have good inhibitory effect.Part 3,we adopted unilateral renal ligation+intake of high-sugar-high-fat diet and intraperitoneal injection of 2%STZ to establish rat model of diabetic nephropathy in this experiment to observe the effect of Qi Kwai Granules on the protection of diabetic nephropathy(DN)rats and to evaluate the protective effect of Qi Kwai Granules against renal injury of diabetic nephropathy.The blood glucose and 24h urine volume,urinary albumin,creatinine(UCr),urine glucose(GLU)content were tested;the determination of urea nitrogen(BUN).Serum creatinine(SCr),cholesterol(CHOL),triglyceride(TG)were also measured;creatinine clearance rate(CCr)and urinary protein excretion rate(UAER)were calculated;the determination of serum interleukin 6(IL-6)content were observed by enzyme-linked immunosorbent assay(ELISA).HE staining of renal tissue changes were observed by pathological examination,the expressions of MCP-1 and TGF-β1 in renal tissue were evaluated by immunohistochemistry method to assess the protective effect of Qi Kwai Granules on rats with diabetic nephropathy and to explore its protection mechanism of renal injury.Results:Qi Kwai Granules can improve the symptoms of diabetic nephropathy rats.The blood glucose,GLU,CHOL,TG,24h urine volume,urinary albumin urine protein excretion rate and serum creatinine levels of Qi Kwai Granules in each group were significantly lower;urinary creatinine(UCr)and creatinine clearance rate(CCr)of Qi Kwai Granules high,medium,low groups were increased significantly,the contents of IL-6 in Qi Kwai Granules high,medium,low groups rats serum were obviously reduced;the expressions of MCP-1 and TGF-β1 in renal tissue are low compared with the DN model group(P<0.05,P<0.01).Qi Kwai Granules have good protective effect on diabetic nephropathy.Qi Kwai Granules can reduce blood sugar,improve blood lipid,decrease urinary albumin,relieve the pathological injury of kidney organization;its protective mechanisms may be related to the down-regulation of IL-6 and inhibition of the expression of MCP-1 and TGF-β1 in diabetic nephropathy rats. |
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