ABSTRACT
Objective To observe the effect of liver acquired expression of apobec-1 on blood lipid metabolism, hepatic low density lipoprotein receptor (LDLR), and hepatic low density lipoprotein receptor related protein (LRP) in nephrotic syndrome(NS) rabbits and to explore the lipid-lowering effect and possible mechanism.Methods Thirty healthy ordinary level male new Zealand rabbits were randomly divided into 3 groups:sham operation group (n =10), N S group (n =10), and apobec-1 treatment group (n =10).Adaptive feeding was given for 1 week, then NS group and apobec-1 treatment group underwent left nephrectomy,and 1 week later,adriamycin (4 mg/kg) was used to construct the NS model by way of ear vein injection.In the 11th week after operation, apobec-1 recombinant adenovirus (1 × 1013 virus/kg) was injected through ear vein in apobec-1 treatment group.The 12th week after operation, all rabbits were sacrificed.Right kidney, liver, blood and 24 hour urine were collected.In 3 groups, 24 hour urinary protein (24UPr), albumin (Alb), blood urea nitrogen (BUN), creatinine (Cr), blood lipid were detected.Renal pathology was observed by means of HE staining.Expressions of liver LDLR, LRP were observed by using Western blot.Results (1) There were significant differences among the 3 groups in 24UPr (F =42.778, P =0.000), Alb (F =3.819, P =0.034), BUN (F =6.562, P =0.005), Cr (F =16.076, P =0.000), total cholesterol (TC) (F =17.531, P =0.000), total triglyceride (TG) (F =6.192, P =0.006), very low density lipoprotein (VLDL-C) (F =6.192, P =0.006), low density lipoprotein (LDL-C) (F =34.924, P =0.000) and apolipoprotein B100 (ApoB100) (F =5.180, P =0.012) and apolipoprotein B48 (ApoB48) (F =6.161, P =0.006).(2) Compared with the sham operation group, NS group showed that 24UPr, BUN, Cr, TC, TG, VLDL-C, LDL-C, ApoB100 increased, but Alb decreased, and there was statistical significance (all P ＜ 0.05).(3) Compared with NS group, apobec-1 treatment group showed that TC, TG, VLDL-C, LDL-C, ApoB 100, ApoB48 decreased, and there were statistical significances (all P ＜ 0.05).(4) Compared with the sham operation group, apobec-1 treatment group showed that 24UPr, BUN, Cr increased, but Alb, apolipoprotein B48 (ApoB48) decreased, there were statistical significances (all P ＜ 0.05).(5) There were significant differences of hepatic protein expression among the 3 groups in LRP (F =44.180, P =0.000), LDLR (F =63.141 ,P =0.000).Compared with the sham operation group and NS group, apobec-1 treatment group showed that the expression of LRP was up-regulated (P ＜ 0.01,0.05), while the expression of LDLR was down-regulated (all P ＜ 0.05).Conclusions When liver acquired expression of apobec-1 in NS, it could up-regulate LRP,accelerate the elimination of ApoB48-lipoproteins, and produce a certain lipid-lowering effect.
ABSTRACT
Objective To explore the effect of the liver acquired expression of apolipoprotein B editing catalytic polypeptide-1 (Apobec-1) on hyperlipidemia of renal disease. Methods Thirty healthy ordinary level male New Zealand rabbits were randomly divided into three groups: sham operation group, nephropathy group, and Apobec-1 treatment group (Each group has 10 rabbits). Adapt feeding for one week, nephropathy group and Apobec-1 treat-ment group underwent left nephrectomy, and one week later, adriamycin (4 mg / kg) was used to construct the ne-phropathy model by ear vein injection. The eleventh week after operation, apobec-1 recombinant adenovirus (1 × 1013 Virus/ kg) was injected by ear vein in apobec-1 treatment group. The twelfth week after operation, all rabbits were sacrificed. Right kidney, liver, blood and 24h urine were left. In three groups, 24 hour urinary protein (24UPr), albumin (Alb), blood urea nitrogen (BUN), creatinine (Cr), blood lipid were detected. Renal pa-thology was observed by HE staining. Expressions of liver apobec-1, apolipoprotein B48(ApoB48)were observed by Western blot. Results ① Compared with the sham operation group, nephropathy group showed that 24UPr, BUN, Cr, total cholesterol (TC), total triglyceride (TG), very low density lipoprotein (VLDL-C), low density lipoprotein (LDL-C), apolipoprotein B100 (ApoB100) were increased(P < 0. 05), but Alb was decreased(P <0. 05). ② Compared with the nephropathy group, Apobec-1 treatment group showed that TC, TG, VLDL-C, LDL-C, ApoB100, ApoB48 were decreased(P < 0. 05). ③ Compared with the sham operation group, Apobec-1 treat-ment group showed that 24UPr, BUN, Cr were increased( P < 0. 05), but Alb, ApoB48 were decreased( P <0. 05). ④ Compared with the sham operation group and nephropathy group, Apobec-1 treatment group showed that the expression of Apobec-1 and ApoB48 were up-regulated (P < 0. 01). Conclusion When liver aquires expres-sion of Apobec-1 in hyperlipidemia of renal disease, it can reconstruct ApoB mRNA, increase the synthesis of ApoB48-lipoprotein, and play a certain lipid-lowering effect.
ABSTRACT
Objectives To study the expression features of C-type natriuretic peptide (CNP)/natriuretic peptide receptor-B (NPR-B) axis and two parallel elimination pathways, natriuretic peptide receptor-C (NPR-C) and neutral endopeptidase (NEP) in unilateral ureteral obstruction (UUO) rats. Methods CNP, NPR-B, NPR-C, NEP, Col-IV and type IV collagen (Col-IV) mRNA and proteins were determined by in situ hybridization, real-time PCR, immunohistochemistry and western blot in UUO rats at 24h, 72h, 1w, 2w, 3w, 1m, 2m and 3m. Results CNP expression tended to be higher immediately after ligation and de-clined along with the progression of disease, occurring predominantly in tubular epithelial cells. A high-level CNP may attribute to the elevated expression of NPR-B in the early phase of UUO. Conclusions NEP and NPR participate in the regulation of CNP expression in tubulointerstitial fibrosis. The gradual increased expression of NPR-C and NEP may cause the subsequent de-cline of CNP.