Division of Nephrology, The Second Xiangya Hospital, Research Institute of Nephrology, Central South University, Changsha, PR China.
Ren Fail. 2011;33(2):233-41. doi: 10.3109/0886022X.2011.553305.
To investigate the effects of norcantharidin (NCTD) on tubulointerstitial fibrosis of diabetic nephropathy (DN) in streptozotocin-induced rat model.
Sprague-Dawley rats were randomly divided into control group, model group, low-dose NCTD (0.05 mg/kg/day) group, and high-dose NCTD (0.1 mg/kg/day) group. The model group was induced by injection intraperitoneally with 30 mg/kg streptozotocin in 0.1 mol/L sodium citrate solution (pH 4.5), after high-calorie foods were given for 2 months. NCTD was administered daily after the DN rat model was built. Rats were sacrificed at the end of the third and the eighth week; renal fibrosis and the expression of FN, collagen IV, TGF-β1, and calcineurin (CaN) were detected by Masson and immunohistochemistry staining, respectively.
Tubulointerstitial fibrosis was observed in DN rats, this kind of pathological changes was ameliorated in NCTD treatment group (p < 0.05). The expressions of FN, collagen IV, and TGF-β1 protein increased in the tubulointerstitial field of DN rats compared with the rats in control group. NCTD treatment could dose-dependently decrease their expression and reverse the fibrotic degree (p < 0.05). Meanwhile, the expression of CaN was detected in tubular fields of normal kidney and increased in the tubulointerstitial field in DN rats. However, NCTD downregulated its expression in a dose-dependent manner (p < 0.05).
NCTD could downregulate FN, collagen IV, and TGF-β1 expression in tubulointerstitial fields and attenuate tubulointerstitial fibrosis in the early stage of DN rats. NCTD also alleviated the expression of CaN in tubules in DN. The relationship between the role of NCTD's anti-tubulointerstitial fibrosis and its inhibition to CaN expression remains to be further elucidated.
探讨去甲斑蝥素（NCTD）对链脲佐菌素诱导的糖尿病肾病（DN）大鼠模型小管间质纤维化的影响。
将 Sprague-Dawley 大鼠随机分为对照组、模型组、低剂量 NCTD（0.05 mg/kg/天）组和高剂量 NCTD（0.1 mg/kg/天）组。模型组大鼠以 0.1mol/L 柠檬酸钠溶液（pH4.5）中的 30mg/kg 链脲佐菌素腹腔注射诱导，给予高糖食物 2 个月后。DN 大鼠模型建立后，每天给予 NCTD 治疗。在第 3 周和第 8 周末处死大鼠；采用 Masson 和免疫组化染色法检测肾纤维化和 FN、IV 型胶原、TGF-β1 和钙调神经磷酸酶（CaN）的表达。
DN 大鼠出现小管间质纤维化，NCTD 治疗组这种病理变化得到改善（p<0.05）。与对照组大鼠相比，DN 大鼠小管间质区 FN、IV 型胶原和 TGF-β1 蛋白表达增加。NCTD 治疗可剂量依赖性降低其表达并逆转纤维化程度（p<0.05）。同时，正常肾组织的管状区域检测到 CaN 的表达，并在 DN 大鼠的小管间质区域增加。然而，NCTD 以剂量依赖的方式下调其表达（p<0.05）。
NCTD 可下调小管间质区 FN、IV 型胶原和 TGF-β1 的表达，减轻早期 DN 大鼠的小管间质纤维化。NCTD 还减轻了 DN 大鼠肾小管中 CaN 的表达。NCTD 抗小管间质纤维化作用与其对 CaN 表达的抑制作用之间的关系有待进一步阐明。
