Sun Wen, Zhu Zhi, Yu Jian, Wang Yong-hong, Xiong Man, Gao Xia, Zhao Zhong-hua, Liu Xue-guang
Department of Traditional Chinese Medicine, Fudan University, Shanghai 201102, China.
Zhong Xi Yi Jie He Xue Bao. 2011 May;9(5):546-52. doi: 10.3736/jcim20110513.
To investigate the effects of Huaiqihuang Granule, a compound Chinese herbal medicine, on expressions of nephrin and podocin of slit diaphragm of glomerular podocytes in rats with adriamycin-induced nephrosis and to explore the mechanism in reducing the proteinuria.
Twenty SD rats were randomly divided into five groups: control group, model group, glucocorticoid group, Huaiqihuang Granule group and Huaiqihuang Granule plus glucocorticoid group. The 24-hour urine was collected 7, 14, 21 and 28 days after adriamycin injection respectively to measure 24-hour urinary protein, and all rats were sacrificed after 28-day treatment. Pathological changes in renal tissues were observed under a light microscope and an electron microscope. Expressions of nephrin and podocin mRNAs in renal cortex were determined by real-time polymerase chain reaction, and protein levels of nephrin and podocin were detected by Western blotting.
(1) In the model group and the treatment groups, the level of urinary protein increased significantly from the 14th day. (2) Under the light microscope, inflammatory cells and slight fibroplasia were found in renal interstitium of the model group, but there were less inflammatory cells in renal interstitium in the intervention groups than in the model group. Under the electron microscope, 29 days after adriamycin injection, extensive fusion of foot processes was observed. (3) The expressions of nephrin and podocin were higher in treatment groups than in the model group. (4) Proteinuria level was negatively correlated with the expressions of nephrin mRNA and nephrin and podocin proteins.
The above results indicate that Huaiqihuang Granule can maintain the integrity of the slid diaphragram in podocyte, alleviate the lesion of glomerular filtration membrane, and decrease the proteinuria by up-regulating the expressions of nephrin and podocin. Huaiqihuang Granule plus glucocorticoid maybe has better effects than glucocorticoid alone.
研究中药复方制剂槐杞黄颗粒对阿霉素肾病大鼠肾小球足细胞裂孔隔膜蛋白nephrin和podocin表达的影响,探讨其减少蛋白尿的作用机制。
将20只SD大鼠随机分为5组:对照组、模型组、糖皮质激素组、槐杞黄颗粒组、槐杞黄颗粒联合糖皮质激素组。阿霉素注射后7、14、21、28天分别收集24小时尿液,检测24小时尿蛋白,治疗28天后处死所有大鼠。光镜和电镜下观察肾组织病理变化。采用实时聚合酶链反应检测肾皮质nephrin和podocin mRNA的表达,蛋白质免疫印迹法检测nephrin和podocin蛋白水平。
(1)模型组及各治疗组尿蛋白水平自第14天起显著升高。(2)光镜下,模型组肾间质有炎性细胞浸润及轻度纤维组织增生,各干预组肾间质炎性细胞较模型组减少。电镜下,阿霉素注射29天后可见足突广泛融合。(3)各治疗组nephrin和podocin的表达高于模型组。(4)蛋白尿水平与nephrin mRNA、nephrin和podocin蛋白的表达呈负相关。
上述结果表明,槐杞黄颗粒可维持足细胞裂孔隔膜的完整性,减轻肾小球滤过膜损伤,上调nephrin和podocin的表达,从而减少蛋白尿。槐杞黄颗粒联合糖皮质激素可能比单用糖皮质激素效果更好。