Effect Of Hyperhomocysteine On The Renal Damage Of Hypertensive Rats And The Mechanism Offolic Acidintervention

Objective: This study was performed through establishing a rat model of hypertension with hyperhomocysteine(HHcy),to observe the relationship between HHcy and renal damage.Moreover,we explore the effects of folic acid on the renal damage,by observing indicators of endoplasmic reticulum stress.Methods: First part.8 Wistar-Kyoto rats(WKY)and 32 spontaneously hypertension rats(SHR)were selected.Those were divided into three groups,8 WKY double distilled water group,8 SHR double distilled water group and 24 SHR 2% methionine water group.In one month,SBP,DBP,plasma homocysteine,creatinine and microalbumin of urine was tested.Second part.24 SHR with HHcy were selected from the first part.These rats were randomly divided into three groups,control group,enalapril group,enalapril folic acid group.After two months,SBP,DBP,plasma homocysteine,creatinine and microalbumin of urine was tested,and changes of renal structure,the expression of glucose regulated protein 78,C/CEP homologous protein,podocyte proteinnephrin in renal tissue were observed.Result: First part.(1)Compared with SHR double distilled water and WKY double distilled water group,SHR 2% methionine water group was higher in SBP and DBP(P<0.01);Compared with WKY double distilled water group,SHR double distilled water was higher in SBP and DBP(P<0.05).(2)Compared with SHR double distilled water and WKY double distilled water group,SHR 2% methionine water group was higher in homocysteine(Hcy)and urinary albumin to creatinine ratio(UACR)(P<0.01);Compared with WKY double distilled water group,SHR double distilled water was higher in UACR(P<0.01),but there were no significance between two groups in Hcy.Second part.(1)Compared with control group,enalapril and enalapril folic acid group were lower in SBP,UACR and Hcy(P<0.05).Compared with enalapril folic acid group,enalapril group was higher in Hcy(P<0.05),but there were no significance between two groups in SBP and UACR.(2)The results of HE staining showed that: glomerular structural was integrity in enalapril folic acid group,mild atrophy in enalapril group,moderate atrophy in control group;(3)The results of RT-PCR showed that: compared with control group,enalapril and enalapril folic acid group were lower in the expression values of chop and grp78 m RNA(P<0.05),higher in the expression values of nephrin m RNA(P<0.05);There were no differences in the expression values of chop and grp78 m RNA between enalapril and enalapril folic acid group(P>0.05);But the expression values of nephrin m RNA was higher in enalapril folic acid group than that in enalapril group(P<0.05).(4)The results of Western blot showed that: compared with control group,enalapril and enalapril folic acid group were lower in the gray values of chop,grp78 and nephrin(P<0.05);There were significant differences in the gray values of nephrin(P<0.05),and no differences in the gray values of chop and grp78(P>0.05)between enalapril and enalapril folic acid group.Conclusion: 1.Homocysteine can increase SBP of hypertensive rats and aggravate hypertensive renal damage.2.Folic acid can decrease the levels of SBP,Hcy and UACR in hypertensive rats with hyperhomocysteinemia and alleviate podocyte injury,which is independent of apoptotic pathway pathway caused by endoplasmic reticulum stress.