| ObjectiveFollowing the previous work of our group,in order to further expl ore the therapeutic mechanism of Fushengong prescreption on CRF,this stuy tended to studied the "regulation-antagonism" effect of Fushengon g prescreption on ACE-AngⅡ-AT1 R axis and ACE2-Ang(1-7)-MAS R axis in adenine-induced CRF in rats,and to explore the mechanism of delaying the progression of CRF.MethodThe CRF model was replicated by intragastric administration of0.25 g.kg-1d-1 adenine suspension for 28 days,and the normal group was intragastrically administered with an equal volume of normal sa line.After 28 days,the successfully modeled rats were divided into model group,benazepril group,and low-dose,middle-dose and high-d ose groups of Fushengong prescreption group with corresponding dos es of drug intervention for 28 days.After the above operation,the data of tail vein systolic blood pr essure(SBP)and diastolic blood pressure(DBP)were collected.24-h our urine was collected by metabolic cage to determine 24-hour urine protein(24 h U-pro).Serum and kidney tissue were collected from all rats.The data of creatinine(Scr)and urea nitrogen(BUN)in seru m were collected,and the renal tissue embedded in paraffin was sect ioned,the histological morphology was observed by Hematoxylin eosi n(HE)staining,and the degree of renal interstitial fibrosis was obse rved by Masson staining.The levels of AngⅡ、Ang(1-7)and Cystatin C(Cys-C)in serum and renal tissue homogenate were measured by enzyme linked immunosorbent assay(ELISA)).The protein levels of ACE,ACE2,AT1 R and MASR were detected by Western blot.The i mmunohistochemistry were used to detect the expression of ACE and ACE2 protein in renal tissues.ResultsCompared with the normal group,the expression levels of Scr,B UN and Cys-C,24 h U-pro,SBP,DBP in the model group were signi ficantly increased(P<0.05),the content of AngⅡ in serum and kidney tissues were significantly increased,the content of Ang(1-7)were si gnificantly decreased(P<0.05),the expression of ACE and AT1 R prot ein in renal tissues were significantly increased(P<0.05),and the expr ession of ACE2 and MASR protein were significantly decreased(P<0.05).Compared with the model group and benazepril group,after the int ervention with Fushengong prescreption,the Scr,BUN,Cys-C of serum,24 h U-pro,SBP,DBP decreased(P<0.05),the content of AngⅡ in ser um and kidney tissues decreased significantly,Ang(1-7)increased sign ificantly(P<0.05),the expression of ACE and AT1 R protein in renal ti ssues decreased significantly(P<0.05),ACE2 and MASR protein incre ased significantly(P<0.05).The high-dose Fushengong prescreption ha s the best effect.The high,medium and low-dose effects of Fushengong prescreption were dose-dependent.ConclusionFushengong prescreption improved renal function and pathological change of kidney in adenine-induced rats with chronic renal failure.Th e mechanism may be related to the inhibition of ACE-AngⅡ-AT1 R axis and promotion of ACE2-Ang(1-7)-MASR axis,which leads to the d elaying in the progression of CRF. |
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