Study On The Level Of Endoplasmic Reticulum Stress In Renal Of Diabetic Kidney Disease Rats And The Intervention Of Traditional Chinese Medicine Therapy

objective: 1.Animal experiment To observe the levels of Endoplasmic reticulum stress related molecules GRP78?Caspase-12 and CHOP in renal of diabetic kidney disease rats.2.Clinical Trials To investigate the treatment effect of Qutantongluo Decoction and its mechanism of intervention,and observe its efficacy to the patient of diabetic kidney disease.Method: 1.Animal experiment The diabetic kidney disease rat model was induced by feeding high-glucose high-fat diet in combination with intraperitoneal injection of STZ,We randomly divided wistar rats into4 groups:normal control group?the model group?Qutantongluo Decoction group?4-phenyl butyric acid treatment(PBA group).Qutantongluo Decoction group rats gavage With the dose of 2m L / 100 g,4-PBA rats gavage by 1g / kg daily dose,At the end of 8 weeks,Observing the morphological and blood biochemical changes,such as hemoglobin(Hb),blood urea nitrogen(Bun),creatinine(Scr),and employing various methods such as immunohistochemistry ?Western-blot,to detect the expressions of Endoplasmic reticulum stress-related molecules GRP78 ?Caspase-12 and CHOP in renal of diabetic kidney disease rats.2.Clinical Trials Selected 84 cases of diabetic kidney disease ?-?,were divided into two groups randomly,42 cases inthe Qutan Tongluo Decoction treatment group(the treatment group),42 cases in the control group(the control group),After two months,observed the effects ofurinary albumin excretion(UAE),serum Bun,Scr,Cys C,Hb A1 c.Results: Animal experiment 1.Compared with the control group,the levels of blood glucose and hemoglobin in model group were significantly increased(P< 0.05),After the treatment,The treatment group showed significantly low levels of blood glucose(P<0.05)and hemoglobin(P<0.05),The levels of blood glucose and hemoglobin in Qutan Tongluo Decoction group were lower than that of PBA group(P<0.05).2.The levels of blood urine nitrogen?creatinine and Cys C in the model group were significantly increased compared with the control group(P<0.05),in treatment group,Levels of blood urine nitrogen and creatinine? Cys C after treatment decreased more significantly than model group(P<0.05).The reduction of Qutan Tongluo Decoction after treatment was more significant than that of PBA group(P<0.05).3.The levels of Urinary protein was no significance statistically before treatment(P>0.05),after treatment,the Urinary protein of Qutan Tongluo Decoction group was lower than that of the model group and before treatment(P<0.05)? 4.HE staining found that glomerular structure is normal,there were no obvious thickening of GBM and the change of the MCs quantity in control group;In model group,we observed hypertrophy of renal glomerulus,thickening of GBM,expansion of mesangial matrix and vacuolar degeneration of renal tubular cell,However,treatment with Qutan Tongluo Decoction and 4-PBA reversed these changes to some degree,structure of glomerular and tubular were better than that of model group.The pathomorphology changes of Qutan Tongluo Decoction were better than that of 4-PBA group.5 Immunohistochemistry showed that GRP78 was abundantly expressed in renal tissue of diabetic kidney disease rats,The expression of GRP78 proteins in model group was significantly higher than that of control group,these findings suggested the activation of ER stress in the kidney,Qutan Tongluo Decoction decreased the expression of GRP78 proteins,The result of Westem blot analysis confirmed the finding.Compared with the control group,Western blot showed that the expressions of Caspase-12 and CHOP proteins were higher in model group,Which was Consistent with the results of immunohistochemistry.Immunohistochemistry showed that the distribution and expression of CHOP and Caspase-12 significantly increased in model group,Qutan Tongluo Decoction lower the expression of Caspase-12 and CHOP proteins.Clinical Trials 1.Qutan Tongluo Decoction effectively improved clinical symptoms of the patients with DN(P <0.05).2.In treatment group,the clinical curative effect was92.5%,significantly better than the control group 75%;In treatment group,the levels of serum BUN,SCr,Cys C.decrease,the curative effect was significantly better than the control group(P<0.05).Conclusions: 1.the expression of GRP78?Caspase-12 and CHOP were up regulated in renal of diabetic kidney disease rats,these findings suggested the activation of ER stress in the kidney.2.Qutan Tongluo Decoction lower the expression of GRP78?Caspase-12 and CHOP proteins,improve pathological damage of kidney,slow the progress of renal failure.3.Qutan Tongluo Decoction decreased blood glucose,BUN,SCr,Cys Cand Urinary protein,improve function in renal of diabetic kidney disease rats.4.Qutan Tongluo Decoction improve clinical symptomsof the patients of DN,slow the progress of diabetic kidney disease.