Effect Of Gastric Bypass Surgery On Kidney Function In Diabetic Mellitus Rats And Its Mechanism

Objective:Observe the changes of the blood glucose,blood ureanitrogen(Bun),serum creatinine(Cr),Advanced glycation end products(AGE)and the expression of receptor of AGE(RAGE)、protein kinase C (PKC)-β、protein kinase A(PKA) in the kidney in diabetic mellitus rats after underwentthe gastric bypass surgery(GBP),to explore the effect of gastric bypass surgeryon kidney function in diabetic rats and investigate the mechanism.Method:40SD rats were chosen for experiment and32SD rats were randomly selectedfrom the40rats. The32rats were given one-time intraperitoneal injection ofstreptozotocin(STZ,35mg/kg) and high-fat diet.OGTT was performed a weekafter the injection of STZ,and the rats with the blood glucose greater than11.1mol/L were selected as the diabetic rats.Diabetic rats were divided intothree groups randomly: diabetes group(DG, n=8), sham operation group(SOG,n=8),operation group(OG, n=6),another8normal SD rats were used as thenormal control group(NCG, n=8).Each group rats were treatment asfollows:①DG group and NCG group rats were done not any treatment;②OGgroup rats were treated with gastric bypass surgery;.③The SOG group weretreated with Antroduodenal amputation in situ end to end anastomosis.Theblood glucose,blood Bun, serum Cr and serum AGE were measured at the timesof pre-operation and8weeks after the operation in each group rats,the expressions of RAGE,PKA and PKC-β in renal tissue were measured by RealTime PCR(RT-PCR) and Western blot.The expression of fibronectin in renaltissue were measured by immunohistochemical staining,the deposition of typeIV collagen in kidney tissue were observed by masson staining. Results:Testing the indicators of each group rats,we have the following findings:①8weeks after surgery,the blood glucose level of OG group were significantlylower than pre-operation;Compared with DG group and SOG group,the bloodglucose level of OG group is also significant lower than that in the twogroups(P<0.05),and had no significant difference compared with NCGgroup(P>005).②8weeks after surgery,the blood Bun and the serum Cr level ofOG group were significantly lower than DG group and SOG group(P<0.05),buthad no significant difference with NCG group(P>005).③8weeks aftersurgery,The serum AGE level of DG group and SOG group were significantlyhigher than pre-operation(P<0.05),and higher than that in OG group;The serumAGE level of OG group had no obvious changes compared withpre-operation(P>005),and had no significant difference with NCGgroup(P>005).④The mRNA and protein expression of RAGE and PKC-β ofOG group were lower than DG group and SOG group(P<0.05),and had nosignificant difference with NCG group(P>005).⑤The mRNA and proteinexpression of PKA of OG group were significantly higher than DG group andSOG group(P<0.05).⑥The expression of fibronectin in kidney of OG groupwere lower than DG group and SOG group(P<0.05),and the deposition of type IV collagen in renal tissue of OG group were also lower than DG group andSOG group(P<0.05).Conclusion:①Gastric bypass surgery could reduce the theblood glucose level in diabetic rats;②Gastric bypass surgery could reduce theserum AGE in diabetic rats and decreased the expression of RAGE and PKC-βin the kidney tissue;③Gastric bypass surgery could increased the expression ofPKA in kidney tissue;④Gastric bypass surgery could reduce the oxidative stressand inflammatory reaction in renal tissue and protect the renal function throughthe above-mentioned ways(conclusion2and3).