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目的观察吡格列酮对糖尿病大鼠肾组织骨桥蛋白表达的影响。方法 SD大鼠随机分为正常对照组和造模组。链脲佐菌素诱导糖尿病大鼠。造模成功的大鼠随机分为糖尿病组、吡格列酮3,15 mg·kg-1·d-1组。8周末测大鼠24 h尿微量白蛋白、血糖,血肌酐。HE染色观察肾组织形态,免疫组织化学法及逆转录-聚合酶链反应法分别测大鼠肾组织骨桥蛋白及骨桥蛋白mRNA的表达。结果吡格列酮3 mg·kg-1·d-1组、吡格列酮15 mg·kg-1·d-1组血肌酐、微量白蛋白、肾质量/体质量较糖尿病组明显下降(P<0.05)。与糖尿病组比较,吡格列酮15 mg·kg-1·d-1组血糖明显降低(P<0.05),吡格列酮3mg·kg-1·d-1组血糖无明显改善,差异无统计学意义(P>0.05)。糖尿病组肾组织骨桥蛋白及骨桥蛋白mRNA表达水平较正常对照组明显升高(P<0.05)。吡格列酮3,15 mg·kg-1·d-1组肾组织骨桥蛋白、骨桥蛋白mRNA表达水平较糖尿病组均明显下降(P<0.05)。结论糖尿病大鼠肾组织骨桥蛋白表达增加,提示骨桥蛋白可能参与糖尿病肾脏病变的发病过程。吡格列酮干预可以减少糖尿病大鼠尿微量白蛋白,对肾脏有保护作用。吡格列酮对肾脏的保护作用部分可能与吡格列酮抑制肾脏骨桥蛋白的表达有关。
Objective To observe the effect of pioglitazone on the expression of osteopontin in the kidney of diabetic rats. Methods SD rats were randomly divided into normal control group and model group. Streptozotocin induced diabetic rats. The successful model rats were randomly divided into diabetic group and pioglitazone 3,15 mg · kg -1 · d -1 group. 8-week rat urine microalbuminuria 24 hours, blood glucose, serum creatinine. The morphological changes of renal tissue were observed by HE staining. The expressions of osteopontin and osteopontin mRNA in renal tissue were detected by immunohistochemistry and reverse transcription - polymerase chain reaction. Results Serum creatinine, microalbumin, kidney mass / body weight of pioglitazone 3 mg · kg -1 · d -1 group and pioglitazone 15 mg · kg -1 · d -1 group were significantly lower than those of diabetic group (P 0.05). Compared with diabetic group, the blood glucose of pioglitazone 15 mg · kg-1 · d-1 group was significantly lower (P <0.05), while the blood sugar of pioglitazone 3 mg · kg-1 · d-1 group was no significant difference (P> 0.05). The mRNA expression of osteopontin and osteopontin in diabetic group was significantly higher than that in normal control group (P <0.05). The mRNA expression of osteopontin and osteopontin in 3,15 mg · kg-1 · d-1 pioglitazone group was significantly lower than that in diabetic group (P <0.05). Conclusion The expression of osteopontin in diabetic rats increased, suggesting that osteopontin may be involved in the pathogenesis of diabetic nephropathy. Pioglitazone intervention can reduce urine microalbuminuria in diabetic rats and has a protective effect on the kidney. Part of the protective effect of pioglitazone on the kidneys may be related to pioglitazone inhibiting the expression of osteopontin in the kidney.