Vol. 23 No.17 China Journal of Modern Medicine Jun. 2013 1005-8982(2013)17-0035-05 * 杨 波 1, 邓 薇 1, 颜 天 铭 1, 谢 红 萍 1, 蒋 云 生 2, 段 绍 斌 2 观 察 甲 基 胍 加 重 肾 衰 大 鼠 残 余 肾 功 能 损 害, 以 及 普 罗 布 考 的 干 预 作 用 大 鼠 随 机 分 为 假 手 术 组 A( 正 常 对 照 ) 和 5/6 肾 切 除 肾 衰 模 型 (B C D),B 组 : 给 予 生 理 盐 水 灌 胃 C 组 : 给 予 甲 基 胍 D 组 : 甲 基 胍 + 普 罗 布 考 组, 检 测 各 组 血 清 尿 素 氮 肌 酐, 观 察 肾 脏 组 织 的 病 理 改 变, 免 疫 组 化 法 检 测 肾 组 织 内 转 化 生 长 因 子 (TGF-β 1 ) 结 缔 组 织 生 长 因 子 (CTGF) 纤 维 结 合 蛋 白 (FN) 的 表 达 水 平,TUNEL 观 察 细 胞 的 凋 亡 模 型 组 (B C D) 较 A 组 血 清 尿 素 氮 肌 酐 显 著 升 高 (F =93.355,192.336,P <0.05), 肾 小 球 体 积 增 大 系 膜 细 胞 及 基 质 明 显 增 生, 免 疫 组 化 染 色 显 示 阳 性 面 积 TGF-β 1 CTGF FN 表 达 显 著 增 强 (F =2064. 459,814.527,91.021,P <0.05), 细 胞 凋 亡 率 显 著 增 加 (F=118.97,P <0.05) 加 入 甲 基 胍 后 血 清 尿 素 氮 肌 酐 较 模 型 组 明 显 升 高 (F =93.355,192.336,P <0.05), 肾 小 球 体 积 较 模 型 组 明 显 增 大 系 膜 细 胞 及 基 质 较 模 型 组 增 生 严 重, 免 疫 组 化 染 色 显 示 TGF-β 1 CTGF FN 均 较 模 型 组 表 达 增 强 (F =2064.459,814.527,91.021,P <0.05), 细 胞 凋 亡 率 较 模 型 组 显 著 增 加 (F =2064.459,814.527,91.021,P <0.05), 而 加 入 普 罗 布 考 后 血 清 尿 素 氮 肌 酐 明 显 下 降 (F = 93.355,192.336,P <0.05), 肾 小 球 体 积 小 于 甲 基 胍 组 系 膜 细 胞 及 基 质 增 生 小 于 甲 基 胍 组, 免 疫 组 化 显 示 TGFβ 1 CTGT FN 表 达 减 弱 (F =2064.459,814.527,91.021,P <0.05), 细 胞 凋 亡 率 显 著 降 低 (F =118.97,P <0.05) 甲 基 胍 可 促 进 肾 衰 大 鼠 残 余 肾 细 胞 的 凋 亡 和 纤 维 化 相 关 因 子 的 表 达, 普 罗 布 考 有 一 定 的 拮 抗 作 用 慢 性 肾 功 能 衰 竭 ; 甲 基 胍 ; 普 罗 布 考 ; 纤 维 化 ; 凋 亡 R692.5 A Study of the inhibition effect of Probucol on increased renal impairment to residual renal function by methylguanidine * YANG Bo 1, DENG Wei 1, YAN Tian-ming 1, XIE Hong-ping 1, JIANG Yun-sheng 2, DUAN Shao-bin 2 (1.Department of Nephrology, the First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R.China; 2.Department of Nephrology, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R.China) Abstract: Objective To study the inhibition effect of Probucol on increased renal impairment by methylguanidine to chronic renal failure rats. Methods Rats were randomly assigned to sham operation group A and the operation group. Rats in the operation group were prepared with 5 / 6 nephrectomy to induce renal failure, then rats were divided into three groups: control group B, methylguanidine group C and methylguanidine-probucol group D. Group A were given routine feed and served as normal control; Group B were given the same amount of saline to feed; Group C were administered with 4 mg kg -1 d methylguanidine; Group D were administered with 4 mg kg -1 d methylguanidine and 500 mg kg -1 d Probucol. Urine protein (Up) and serum BUN, creatinine (Cr) were measured. Renal pathology changes were evaluated. Immunohistochemistry were used to examine the expression of transforming growth factor (TGF-β 1 ), connective tissue growth factor * 35
(CTGF) and fibronectin (FN) in renal tissue. The apoptosis of cell in the renal tissue were observed by TUNEL. Results Compared to the sham group, things are diffierent in model group: serum urea nitrogen and creatinine was significantly increased (P <0.05); HE staining showed the increases of the glomerular volume and the apparent proliferation of mesangial cells and matrix; immunohistochemical staining showed the strong expression of TGF-β 1, CTGT, and FN (P <0.05) by TUNEL staining and the apoptosis rate increased significantly (P <0.05). After adding methyl guanidine, serum urea nitrogen, creatinine was significantly increased (P <0.05) compared to the model group, HE staining showed that the glomerular volume was significantly increased compared with the model group, the proliferation of mesangial cells and matrix is more serious than in the model group, immunohistochemistry staining showed that TGF-β 1, CTGT, FN had a increased expression (P <0.05) compared to the model group, TUNEL staining showed the apoptotic rate was significantly increased (P <0.05) compared to the model group. After adding the Probucol, serum urea nitrogen, creatinine decreased significantly (P <0.05), biopsy showed the decreases of the glomerular volume and the apparent ease of mesangial cells and stromal hyperplasia, immunohistochemistry staining showed the expression of TGFβ 1, CTGT and FN weakened (P <0.05), TNNEL staining showed that apoptosis rate was significantly lower (P <0.05). Conclusion Methylguanidine can stimulate the expression of fibrosis-related factor and the apoptosis of cells in the chronic renal failure rats. Probucol can inhibit the effect of Methylguanidine. Key words: chronic renal failure; methylguanidine; Probucol; fibrosis; apoptosis β ~μ β ± β x± ~ 36
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