| Objective:To study the effect of Astragaloside Ⅳ on the expression of Urotensin II and its receptor(G protein-coupled receptor 14)in renal tissue of rats with diabetic nephropathy.Methods:In 40 healthy SD rats,30 were randomly selected to develop DN model by intritoneal injection of Streptozotocsin(STZ),and the rest 10 were normal group.After modeling,30 rats were randomly divided into DN group,AS-Ⅳ group and losartan potassium group,with 10 rats in each group.As-iv group was given AS-Ⅳ(40mg/kg/d)intragastric administration,losartan potassium group was given losartan potassium(30mg/kg/d)intragastric administration for 8 weeks.Normal group and DN group were given normal saline intragastric for 8 weeks.Body weight,random blood glucose and24 h urinary protein were measured at week 0,4 and 8.8.Serum creatinine(Scr),Blood urea nitrogen(BUN),Triglyceride(TG)and Total cholesterol(TC)were measured at the end of the week.HE and PAS staining were performed to observe histopathological changes.The expression of UII and its receptor GPR14 in renal tissue was observed by immunohistochemistry.Results:1.General situation and survival of rats in each group: rats in the normal group had shiny hair color,smooth texture,moderate activity,good spirit and stable weight gain;In DN group,activity decreased,water intake and urine volume increased significantly,stool quality was thin,spirit was depressed,body weight was decreased,hair color was dark,texture was rough,hair removal was obvious,hair was sparse;The symptoms and signs of AS-Ⅳ and losartan potassium groups were alleviated to varying degrees,but they were still worse than the normal group.During the whole experiment period,the survival of rats in each group was as follows: all rats in the normal group survived;In the DN group,8 rats survived(1 died at week 2 and 4 respectively).In AS-Ⅳ group,9 rats survived(1 died in this group at week 6);There were 9 survivors in the losartan potassium group(1 died in the group at week 7).2.Quantitative results of blood glucose,body weight and 24 h urinary protein of rats in each group: at week 0,4 and 8,the blood glucose level of DN group,AS-Ⅳ group and losartan potassium group was significantly higher than that of normal group(P<0.05),at the end of the 4th week,there was no significant difference in blood glucose level between AS-Ⅳ group and losartan potassium group compared with DN group(P>0.05),but at the end of the 8th week,blood glucose in both groups was lower than that in DN group(P<0.05);At week 0,4 and 8,the body weight of DN group was significantly lower than that of normal group(P<0.05)body weight of AS-Ⅳ group and losartan potassium group was significantly higher than that of DN group at the end of week 4 and8(P<0.05);At the end of week 0,4 and 8,24 h urinary protein level in DN group,AS-Ⅳ group and losartan potassium group was significantly higher than that in normal group(P<0.05),compared with DN group,24 h urinary protein quantification in AS-Ⅳ group and losartan potassium group was decreased to varying degrees(P<0.05)3.Results of Scr,BUN,TG and TC in serum of rats in each group: at the end of 8th week,the levels of Scr,BUN,TG and TC in DN group,AS-Ⅳ group and Losartan potassium group were higher than those in normal group(P<0.05),compared with DN group,the above indexes in AS-Ⅳ group and losartan potassium group had different degrees of decrease(P<0.05).4.Histopathological staining: compared with the normal group,some renal tubules in the DN group were disordered,epithelial cells were swollen,vacuolar degeneration,lumen diameter was reduced,some glomerulus hypertrophy,mesangial matrix was significantly increased,and mesangial area was widened.The above pathological changes were alleviated to varying degrees in AS-Ⅳ group and losartan potassium group.5.Immunohistochemical results showed that the expression of UII and GPR14 in renal tubules in DN group was significantly higher than that in normal group(P<0.05);after AS-Ⅳ and losartan potassium intervention,the expression of UII and GPR14 in AS-Ⅳ and losartan potassium groups also decreased(P<0.05),but still higher than the normal group(P<0.05).Conclusion:AS-Ⅳ may alleviate renal tissue injury and delay renal function progression in DN rats by reducing the expression of UII and GPR14 in DN renal tissue. |
