Effects of adiponectin for diabetic nephropathy

在这项研究中，我们在体外和体内研究了脂联素是否会抑制糖尿病肾病的进展。肾小球系膜细胞增殖在进行性肾小球损伤的发病机制中起着早期和关键的作用。因此，我们首次证明脂联素抑制抵抗素诱导的大鼠肾小球系膜细胞DNA合成(通过[~3H]-胸腺嘧啶核苷掺入法)。与胸腺嘧啶核苷掺入数据一致的是，脂联素降低了抵抗素诱导的MAPK的磷酸化。接下来，我们通过静脉注射腺病毒(Ad-Adipo)过表达脂联素蛋白，研究了脂联素在实验性糖尿病大鼠糖尿病肾病中的作用。雄性Wistar大鼠，。6周龄，使用的是。糖尿病大鼠用链脲佐菌素(STZ)80 mg/kg在pH 4.5的柠檬酸盐缓冲液中腹腔注射复制糖尿病模型。注射STZ后10周，静脉注射Ad-LacZ或Ad-Adipo。注射后3周观察脂联素对尿蛋白排泄的影响。两组大鼠体重、空腹血糖、空腹胰岛素水平、总胆固醇水平、高密度脂蛋白胆固醇水平、血肌酐水平无显著差异，但尿蛋白/肌酐消耗比显著增加25%。在肾脏中，与Ad-LacZ大鼠相比，肾组织中转化生长因子-α的表达显著降低，而I型和IV型胶原的表达在两组间无差异。另外，Ad-Adipo组大鼠肾脏Nehrin mRNA表达显著增加。值得注意的是，与Ad-LacZ大鼠相比，Ad-Adipo大鼠肾脏iNOS、ET-1和PAI-1mRNA表达显著增加，而eNOS mRNA表达显著增加，提示脂联素对糖尿病肾病的预防作用，提示脂联素是一种潜在的治疗策略。

In this study, we investigated whether adiponectin would inhibit the progression of diabetic nephropathy in vitro and in vivo. The mesangial cell proliferation appears to play an early and pivotal role in the pathogenesis of progressive glomerular injury. Therefore, we first demonstrated the adiponectin inhibited resistin-induced DNA synthesis as measured by [3H]-thymidine incorporation on rat cultured mesangial cells. Consistent with the thymidine incorporation data, adiponectin diminished the resistin induced phosphorylation of MAPK.Next, we investigated the effect of adiponectin on diabetic nephropathy in experimental diabetic rats by overexpression the adipinectin protein using intravenous administration of an adenovirus (Ad-Adipo). Male Wistar rats,. 6-week-old, were used. Diabetic rat was induced by intraperitoneal injection of streptozotocin (STZ) (80 mg/kg) in citrate buffer (pH 4.5). At 10 weeks after the STZ injection, Ad-lacZ or Ad-Adipo was injected intravenous. The effects of adiponectin on urinary protein excretion were observed after 3 weeks post Ad injection. Body weight, plasma fasting glucose levels, plasma fasting insulin levels, total cholesterol levels, HDL-cholesterol levels, and plasma creatinine levels are no difference between two groups, whereas and urinary protein/creatinine exertion ratio levels were significantly determined by 25%.In kidney, TGF-a mRNA expression was significantly decreased in the Ad-Adipo rats compared with Ad-lacZ rats, whereas collagen type I and IV mRNA expression were no difference between two groups. In addition, nehrin mRNA expression in kidney was significantly increased in the Ad-Adipo rats. Interestingly, iNOS, ET-1, and PAI-1 mRNA expression were significantly increased, whereas eNOS mRNA expression was in kidney with the ad-Adipo rats compared with Ad-lacZ rats.These results suggest a role of adiponectin in the prevention of diabetic nephropathy and show that adiponectin is a potential therapeutic strategy.