Geng Wenjia, Wei Ribao, Liu Shuwen, Tang Li, Zhu Hanyu, Chen Pu, Wu Jie, Zhang Xueguang, Zhu Fei, Yin Zhong, Chen Xiangmei
Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, People's Republic of China.
Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China.
Biol Res. 2016 Mar 11;49:17. doi: 10.1186/s40659-016-0078-3.
In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH).
Thirteen weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined at the time point of 24 h. Meanwhile, the expression levels of p-Erk1/2, cyclin D1 and p21 at the renal cortex were also tested. The levels of urinary proteins and total cholesterol in the blood were significantly reduced in rats treated with any drug tested in this study. The level of triglyceride was significantly reduced in all three Shenhua Tablet-treated groups. Renal pathomorphological scores were significantly improved in groups of Irb, SHM and SHH. Mesangial cell proliferation was significantly inhibited in any drug-treated group. p-Erk1/2 and cyclin D1 were downregulated whereas p21 was upregulated in the renal cortex.
Our study indicated that Shenhua Tablet is able to inhibit the abnormal proliferation of mesangial cells and to prevent kidney damage, which is likely associated with downregulation of p-Erk1/2 and reduced activity of its downstream target-cyclin D1.
在中国，系膜增生性肾小球肾炎（MsPGN）是最常见的肾脏疾病之一。在本研究中，我们用肾华片治疗慢性抗 Thy-1 MsPGN 大鼠模型，并评估该药片是否能够保护肾功能。36 只 Wistar 大鼠被随机分为 6 组：（1）假手术组（Sham）；（2）抗 Thy-1 肾炎模型组（Thy-1）；（3）抗 Thy-1 肾炎模型 + 厄贝沙坦治疗组（Irb）；（4）抗 Thy-1 肾炎模型 + 低剂量肾华片组（SHL）；（5）抗 Thy-1 肾炎模型 + 中剂量肾华片组（SHM）；（6）抗 Thy-1 肾炎模型 + 高剂量肾华片组（SHH）。
药物治疗 13 周后，在 24 小时这个时间点对尿蛋白进行定量，并全面检查肾脏病理变化。同时，还检测了肾皮质中 p-Erk1/2、细胞周期蛋白 D1 和 p21 的表达水平。本研究中接受任何一种受试药物治疗的大鼠，其尿蛋白水平和血液中总胆固醇水平均显著降低。在所有三个肾华片治疗组中，甘油三酯水平显著降低。Irb、SHM 和 SHH 组的肾脏病理形态学评分显著改善。在任何药物治疗组中，系膜细胞增殖均受到显著抑制。肾皮质中 p-Erk1/2 和细胞周期蛋白 D1 下调，而 p21 上调。
我们的研究表明，肾华片能够抑制系膜细胞的异常增殖并预防肾脏损伤，这可能与 p-Erk1/2 的下调及其下游靶点细胞周期蛋白 D1 的活性降低有关。
