The Study Of Probucol Intervention Of TGF-β1and HO-1in Renal Tissue Of Diabetic Nephropathy Rats

Objective The pathogenesis of diabetic nephropathy in oxidative stress is considered tobe the center link. Hemeoxygenase-1is a very sensitive indicator of cellular oxidativestress process.When diabetes,HO-1in kidney tissue can be significantly induced,it hasthe role of the oxidation resistance stress, anti-fibrosis,and anti-inflammatory reaction.Transforming growth factor1is the strongest known factor in promoting renalinterstitial fibrosis.Probucol is one of the strongest synthetic antioxidants.Thisexperiment aims to investigate probucol intervent the expression of TGF-1and HO-1on diabetic nephropathy rats and clarify probucol delay renal interstitial fibrosispossible mechanism.Method Fifty male SD rats were randomly divided into experimental group and controlgroup. the experimental group give high sugar and fat feed, and DN rat model wasestablished by intraperitoneal injection of streptozotocin,will be successful modeling34rats were randomly divided into the DN group and PB treatment group. Probucoltreatment group by gavage (500mg/kg.d-1),12weeks of gavage treatment known asmouse and check24h urinary protein of quantitative and urinaryN-acetyl--D-glucosaminidase (NAG), the rats were sacrificed to collect blood toobserve serum biochemical indicators: serum cholesterol (TC), high density lipoprotein(HDL), low density lipoprotein (LDL), serum creatinine (Scr), blood urea nitrogen(BUN), C-reactive protein (CRP). Removal of the kidney line tissue sections observedrenal interstitial fibrosis, HO-1Immunohistochemical detection of renal tissue, theexpression of TGF-1in the RT-PCR detection of TGF-1in renal tissue, HO-1nucleicacid expression. The results obtained using independent sample t-test and within-group differences using a paired t-test, P<0.05was considered statistically significant.Results1. Compared with the NC group, DN group rats have different degrees ofincreased feeding, lack of energy, slow activity, increased urine output, weight loss,body hair messy dull. The more improved PB intervention. PB rats body weight (334.74±31.46) g, DN group (316.68±43.60) g and NC group (523.20±21.54) g at the end ofthe experiment were statistically significant (P <0.05).2.Biochemical indicators：compared with the NC group, each model group, random blood glucose, TC, HDL, Scr,BUN, CRP,24h urine protein quantification and urinary NAG was significantly higher,the difference was statistically significant (P <0.05); PB group the above indicators DNgroup is significantly lower. Compared with NC group, the PB group, DN group HDLsignificantly reduced; PB group HDL higher than the DN group, the difference wasstatistically significant (P <0.05). But no significant difference in the PB group and DNgroup blood sugar.3.Renal tissue pathological changes：under light microscope, NCgroup no glomerular, tubular and interstitial lesions; the DN group the majority ofglomerular area and volume increased significantly, the glomerular basement membranethickening, glomerular mesangial cell proliferation, mesangial area widened part offocal glomerulosclerosis changes; turbidity of some tubular epithelial cells, vacuolardegeneration luminal narrowing; PB group lesions were compared with DN group toreduce some of the glomerular capillary The vascular loop basement membranethickening, renal interstitial inflammatory cells infiltration and fibrosis less (P <0.05).Compared with NC group, DN group, PB group of renal tissue TGF-1expression wasincreased (P <0.05); compared with the DN group PB group, TGF-1expression reduce(P <0.05). Compared with NC group, DN group, the increase in HO-1expression in thePB group kidney tissue compared with the DN group (P <0.05); PB group HO-1expression was significantly increased (P <0.05). 4.Renal tissue TGF-1mRNA and HO-1mRNA expression：compared with NC group,DN group and PB group of renal tissue TGF-1mRNA over-active, but lower than PBgroup and DN group (P <0.05); And NC group comparison, DN group and PB group ofrenal tissue HO-1mRNA, but higher than PB group and DN group (P <0.05).Conclusion1.HO-1、TGF-1in the occurrence and development of diabeticnephropathy may play a role. Probucol can alleviate kidney pathological damage, andits mechanism may be related to its up-regulating HO-1expression, down-regulatingTGF-1expression,and then playing kidney protection.2.Probucol can improve thediabetic nephropathy rats of the general state, which can adjust the blood lipidmetabolism, anti-inflammatory, reduce urinary protein, ameliorate renal tubular damage,delay kidney function deterioration.