甲硫氨酸维B1与丹参酮ⅡA磺酸钠对梗阻性黄疸大鼠血浆肿瘤坏死因子、肾功能及肾组织丙二醛与超氧化物歧化酶的影响

Effects of methionine and vitamin B1 and sodium tanshinone lI A sulfonate on tumor necrosis factor-a in plasma and malondialdehyde, superoxide dismutase in kidney and kidney function of rats with obstructive jaundice

目的观察梗阻性黄疸（OJ）大鼠血浆肿瘤坏死因子-a（TNF-a）、肾功能、肾组织内二醛（MDA）与超氧化物歧化酶（SOD）水平变化及甲硫氨酸维B1（MVB1）与丹参酮ⅡA磺酸钠（STS）对OJ大鼠血浆TNF—a水平、肾功能、肾组织MDA与SOD变化的影响。方法以大鼠胆总管结扎（BDL）为OJ模型，设立假手术组（Sham，n=5），将成功模型随机分为实验对照（EC）组、MVB，组、STS组及MVB，与STS联合（M—S）组，每组n=20，术后1d给BDL大鼠腹腔内注射相应剂量药物至13d，采用放射免疫法测定BDL大鼠2、6、10、14d血浆TNF-a、尿素氮（BUN）、Cr水平及14d肾组织MDA、SOD水平，观察死亡率与肾组织病理学改变。结果Sham组血浆TNF-a、BUN、肌酐（Cr）与肾组织MDA、SOD分别为（0．91±0．18）ug／L、（1．54±0．16）mmol／L、（44．23±4．73）umol／L、（4．54±0．46）nmol／ml、（182．16±12．10）U／ml，BDL后大鼠上述检测指标的变化差异有统计学意义（P〈0．01）；与EC组比较，STS组对血浆TNF—a、BUN、Cr及肾组织MDA、SOD影响差异有统计学意义，MVB，组血浆TNF—a、BUN、Cr水平变化差异有统计学意义；MVB1与STS组比较，对血浆BUN、Cr及肾MDA、SOD水平影响差异有统计学意义；M—S组与MYB1、STS组比较，血浆TNF—a、BUN、Cr与肾组织MDA水平明显下降，SOD水平显著升高（P〈0．01）。光镜F：BDL后大鼠肾小球充血，上皮细胞、内皮细胞、系膜细胞增生，肾小管胆色素沉积，上皮片状坏死，间质炎细胞浸润，MVB1组、STS组、M—S组与EC组比较差异有统计学意义。结论OJ大鼠血浆TNF-a与肾组织MDA水平进行性升高及SOD水平显著下降是导致肾功能损害的重要因素之一，MVB1和STS对OJ大鼠血浆TNF—a水平升高有抑制作用，STS可减少OJ时氧自由基损害作用，STS与MVB，联合应用表现出更有效的抗内毒素血症与改善肾组织缺血缺氧的作用。

Objective To observe changes of kidney function, tumor necrosis factor-a （TNF-a） in plasma and renal superoxide dismutase （SOD） and malondialdehyde （MDA） of rats with obstructive jaundice （OJ） and effects of sodium tanshinone II A sulfonate （STS） and methionine and vitamin B1 （MVB1 ）. Methods Sham-operation group was set up （n = 5）, and OJ models were established by ligation of common bile duct in rats. OJ rats were randomly divided into experimental control group （ EC group,n = 20）, MVB, group （n = 20）, STS group （n = 20） and MVB1 and STS group （M-S group, n = 20）. From 1 st to 13 day, the rate in MVB1 and STS groups were respectively injected with the same volume of isotonic sodium hloride, MVB1 and STS, respectively. The rats in M-S group received MVB1 and STS together. The expression levels of TNF-a, blood urea nitrogen （BUN） and creatinine （Cr） in plasma on the day 2, 6, 10 and 14 after operation, MDA and SOD in the kidney tissue on the day 14 were determined by using radioimmunoassay. The histopathological changes of kidney and mortality rate of rats were observed. Results In sham group, levels of TNF-a, BUN and Cr in plasma and MDA and SOD in the kidney tissue were （0.91 ±0.18） ug/L, （1.54±0.16） mmol/L, （44.23 ±4.73） umol/L, （4.54±0,46） nmol/ml, and （ 182. 16 ± 12. 10） U/ml respectively, In the OJ groups, there was significant changes in the above indicators （P 〈0. 01 ）. As compared with EC group, levels of TNF-a, BUN, Cr and MDA were declined and those of SOD were increased in STS group （P 〈 0. 05）. There was significant changes in TNF-a, BUN and Cr in MVB1 grorp （P 〈0. 05）. There was statistically significnat difference in the levels of BUN, Cr, MDA and SOD between MVB1 and STS groups. Levels of TNF-a, BUN, Cr and MDA in M-S group were markedly lower than those in sham group, MVB1 and STS group （P 〈 0. 01 ）, and levels of SOD were significantly higher. Under the light microscopy, histological examination showed hyperplasia of glomerular capillary endothelial cells, epithelial cells and mesangial cells, patchy necrosis, bile pigment deposition in renal tubules, and inflammatory cell infiltration. There were significant difference in histological changes between EC group with MVB1 , STS, and M-S groups. Conclusion That levels of TNF-a in plasma and MDA in the kidney tissue were rapidly elevated and SOD decreased was one of the most important factors of damaging renal function in OJ rats. MVB1 and STS could restrain the increase of plasma TNF-a in OJ rats. STS has effects of protecting renal tissue in OJ rats from damaging by oxygen-derived free radicals. Combined use of MVB1 and STS exerts the syngistic effects, and the antiendotoxin effects were significantly enhanced.