| Objective: To observe the Conggui Yishen Capsule on diabetic kidney disease(DKD)patients with the clinical curative effect,and the expression of endoplasmic reticulum stress(ERS)related factors GRP78,PERK and CHOP.To probe into the mechanism of action of Conggui Yishen Capsule in the treatment of DKD.Methods:1.Clinical study:60 patients of diabetic kidney disease with both spleen and kidney deficiency syndrome were randomly divided into the control group and the treatment group with 30 cases in each group.The two groups were given diabetes health education,diet and exercise control,hypoglycemic therapy and oral losartan potassium(50mg,qd)as basic treatment perscription.The treatment group was treated with Conggui Yishen Capsule(0.4g/particle,5particle/time,3times/day)besides the basic treatment perscription.The course of treatment was 12 weeks.Before and after treatment,respectively recorded in two groups of patients of TCM syndrome integral,fasting plasma glucose(FPG),2h postprandial blood glucose(2h PG),glycosylated hemoglobin(Hb A1c),serum creatinine(Scr),blood urea nitrogen(BUN),urinary albuminuria to creatatine rate(ACR)and serum AGEs.2.The experiment research:80 male SD rats were fed with common diet for one week to adapt to the environment.10 rats were randomly selected as the blank group and fed with common diet.The remaining 70 rats were fed with high-sugar and high-fat diet as the model group.Four weeks later,rats in the model group were given a single dose of 35 mg/kg streptozotocin(STZ)by intraperitoneally injecting to establish DKD rats model.60 successful modeling rats were randomly divided into the model group,the high and low dose group of Conggui Yishen Capsule and the losartan potassium group with 15 rats in each group.The blank group and the model group were given saline 5ml/kg·d by gavage.The losartan potassium group was given losartan potassium 10mg/kg·d by gavage.The high and low dose group of Chinese medicine were given Conggui Yishen Capsule 1080mg/kg·d and 270mg/kg·d by gavage respectively.Before and after 8 weeks of administration,the general condition,FPG and 24 h urine protein quantitative(24h UP)of rats in each group were observed.After 8 weeks of administration,Samples were taken,blood was collected from the abdominal aorta to detect renal function and serum AGEs.HE staining was used to observe the pathological changes of renal tissue in rats under light microscope.The expression levels of ERS-related factors GRP78,PERK and CHOP in rats renal tissue were detected by Western blot.Results:1.Clinical study results:The total effective rate of the treatment group and the control group were 82.8% and 62.1% respectively,the difference was statistically significant(P<0.05).Compared with before treatment,the TCM syndrome integral in the control group and the treatment group decreased,the difference was statistically significant(P<0.01).After treatment,the levels of FPG,2h PG,Hb A1 c,Scr,BUN,ACR and serum AGEs in the two groups decreased,the difference was statistically significant(P<0.05).After 12 weeks of treatment,compared with the control group,the TCM syndrome integral in the treatment group decreased,the difference was statistically significant(P<0.01).The levels of FPG,2h PG,Hb A1 c,Scr,BUN,ACR and serum AGEs in the treatment group were lower than those in the control group,the difference was statistically significant(P<0.05).2.Animal experiment results:After 8 weeks of administration,compared with the blank group,the weight of rats in the model group and each treatment group decreased(P<0.05).Compared with the model group,the weight of each treatment group increased(P<0.01).Compared with the blank group,the FPG of rats in the model group increased(P<0.01).Compared with the model group,the FPG of the high and low dose of Conggui Yishen Capsule group decreased(P<0.01),while there was no significant difference in the losartan potassium group(P>0.05).Compare with the blank group,Scr,BUN,24 h UP and serum AGEs of rats in the model group increased(P<0.01).Compared with the model group,the above indexes in the treatment group decreased(P<0.05).HE staining light microscope showed that there was no obvious abnormality in the kidney histopathology of rats in the blank group.The model group,glomerular hypertrophy,increase of extracellular matrix,high proliferation of mesangial cells,the glomerular basement membrane became thicker and vacuolar changes of some tubular epithelial cells were observed.The above-mentioned lesions were significantly reduced in the other treatment groups compared with the model group.Western blot results showed that the expression of GRP78,PERK and CHOP in kidney tissue of model group rats increased compared with the blank group(P<0.01),while the expression of GRP78,PERK and CHOP in each treatment group decreased compared with the model group(P<0.01).Conclusions:Conggui Yishen Capsule can improve the clinical symptoms of DKD patients and reduce the damage of renal tissue in DKD rats.The mechanism may be related to inhibiting AGEs production,reducing the expression of ERS-related factors GRP78,PERK and CHOP. |
