阻断T型钙通道可减轻早期糖尿病大鼠的蛋白尿和肾脏病理改变

T-type calcium channel blockage ameliorates proteinuria and renal extraecllular matrix accumulation in experimental diabetic rat

目的 探讨Ｔ型钙通道在实验性糖尿病肾病中的作用。方法 采用单侧肾切除的糖尿病大鼠模型，分别每日灌胃给予Ｔ型钙通道阻滞剂米地尔（Ｍｉｂ），Ｌ型钙通道阻滞剂氨氯地平，血管紧张素转换酶抑制剂西拉普利及Ｍｉｂ与Ｃｉｌ合用（Ｍ＋Ｃ），共４周，并使各药物处理组血压相近（每组ｎ＝６￣８）。结果 Ｍｉｂ Ｃｉｌ和Ｍ＋Ｃ治疗组较末治疗的糖尿病（ＤＭ）组尿白蛋白量明显减少（ＭｉｂＬ：７．６９±１．８７，Ｃｉｌ：５．

Objective To investigate the role of T-type calcium channel in streptozotocin(STZ)induced early diabetic nephropathy. Methods Uninephrectomized, STh (65 mg/kg) -induced diabetic male SD rats were used. In order to reach the same reduction of blood pressure, 30 mg/kg mibefradil [Mib,T-type calcium channel blocker), 30 mg/kg amlodipine (Aml, L-type calcium channel blocker), 10 mg/kg cilazapril (Cil, angiotensin converting enzyme inhibitor), 25 mg/kg Mib and 8 mg/kg Cil(M + C) were delivered daily by gavage from the next day of the intreduction to diabetes and totally for 4 weeks,respectively (n = 6 ~ 8 for each group). Results Compared with the untreated uninephrectomized diabetic group (DM), Mib, Cil and M + C treated rats presented substantially less urinary albumin excretion [Mib:7. 69±1. 87, Cil: 5. 53±1. 45, M + C: 3. 87±10. 88 vs. DM: 17. 67±4. 90, (μg/24 h); P <0. 05,respectively], and lower creatinine clearance rate (Ccr) than DM rats. Pathohistological study revealed that,there were less glomerular matrix, larninin and type Ⅳ collagen in Cil and M + C groups compared with the DM. Meanwhile, the glomerular deposition of laminin and type Ⅳ collagen in Mib treated rats were also remarkably less than those of DM, but still significantly greater than the M + C poup. No apparent impact on albuminuria, glomerular matrix accumulation and collagen Ⅳ deposition in Aml treated diabetic kidney were detected. However, in Aml group it still showed significantly lowered proteinuria, Ccr and less laminin volume. M + C treaed rats had least renal changes in terms of glomerular matrix and type Ⅳ collagen deposition among the diabetic rats. Conclusion T-type calcium channel blockage can reduce albuminuria and renal extrecellular matrix accumulation in experimental diabetic rat, and additional benefit can be achieved by combination with ACE inhibitor, suggesting the different role of T-type calcium channel in pmgression of diabetic nephropathy from that of angiotensin and L-type calcium channel, the mechanism of which needs to be furiher investigated.