Sun L, Li X, Shang L, Zheng Y J
School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan 250062, China; Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China.
Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2020 Jan 20;38(1):13-19. doi: 10.3760/cma.j.issn.1001-9391.2020.01.003.
To investigate the relationship between renal injury and apoptosis in rats with nephrotic syndrome induced by mercury, in order to find out the pathogenesis. Forty-eight healthy male SPF-grade BN (Brown-Norway) rats were divided into the control group and the exposure group by random number table. The nephrotic syndrome was caused by subcutaneous injection of HgCl(2) (1 mg/ml) in the abdominal weight per kg of body weight. The control group was injected with the same volume of NaCl as the exposure group. Some rats were sacrificed on the 14th, 21st, 28th, and 35th days, and the serum kidney injury indicators creatinine (CRE) and urea nitrogen (BUN) were detected, and the renal tissue mercury content was detected; the in situ terminal transferase labeling technology (TUNEL) was detected Apoptosis, immunofluorescence detection of Cyt C content, Western blot detection of mitochondrial pathway apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2) , Bcl-2 related X protein (BAX) , cysteine proteinase 3 (Caspase 3) ], mitogen-activated protein kinase (MAPK) signaling pathway-related proteins[p38 mitogen-activated protein kinase (P38MAPK) , extracellular regulatory protein kinase (ERK) ] expression. Compared with the control group, the BUN content in the serum of rats in the exposure group was significantly increased on days 7, 21, and 28, the CRE content was significantly increased on 21 days, the CRE content was significantly decreased on 28 and 35 days, and the organ coefficient and renal mercury content were 14 to 35 days. Significantly increased, and the differences were statistically significant (<0.05) . Compared with the control group, rats in the exposed group showed increased glomerular stroma, tubule dilatation and other renal cell apoptosis at 14 to 35 days, and Cyt C expression was obvious in the exposed groups at 14, 21 days. Compared with the control group, the BAX content of the rats in the exposed group was significantly increased on the 21st day, the content of Caspase 3 in the rats on the 14th and 21st days was significantly increased, and the content of the P38MAPK in the 35th day was significantly increased (<0.05) . HgCl(2) may cause renal cell damage through the mitochondrial pathway of apoptosis and cause nephrotic syndrome, and the MAPK signaling pathway may regulate this process and exert an inhibitory effect on apoptosis.
为探讨汞诱导的肾病综合征大鼠肾损伤与细胞凋亡的关系，以明确其发病机制。将48只健康雄性SPF级BN（布朗-挪威）大鼠按随机数字表法分为对照组和暴露组。通过皮下注射每千克体重1mg/ml的HgCl₂诱导肾病综合征，对照组注射与暴露组相同体积的NaCl。分别于第14、21、28和35天处死部分大鼠，检测血清肾损伤指标肌酐（CRE）和尿素氮（BUN），并检测肾组织汞含量；采用原位末端转移酶标记技术（TUNEL）检测细胞凋亡，免疫荧光检测细胞色素C（Cyt C）含量，蛋白质免疫印迹法检测线粒体途径凋亡相关蛋白[B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（BAX）、半胱氨酸蛋白酶3（Caspase 3）]、丝裂原活化蛋白激酶（MAPK）信号通路相关蛋白[p38丝裂原活化蛋白激酶（P38MAPK）、细胞外调节蛋白激酶（ERK）]的表达。与对照组相比，暴露组大鼠血清BUN含量在第7、21和28天显著升高，CRE含量在第21天显著升高，第28和35天显著降低，脏器系数和肾汞含量在第14至35天显著升高，差异均有统计学意义（<0.05）。与对照组相比，暴露组大鼠在第14至35天出现肾小球基质增多、肾小管扩张等肾细胞凋亡现象，且在第14、21天Cyt C表达明显。与对照组相比，暴露组大鼠在第21天BAX含量显著升高，第14和21天Caspase 3含量显著升高，第35天P38MAPK含量显著升高（<0.05）。HgCl₂可能通过凋亡的线粒体途径导致肾细胞损伤并引发肾病综合征，MAPK信号通路可能调节这一过程并对细胞凋亡发挥抑制作用。
