摘要
目的通过建立单侧输尿管梗阻（UUO）大鼠模型，观察硫化氢（H：s）对肾间质纤维化和单核／巨噬细胞表面特异性标志抗原（ED-1）和肾损伤分子-1（KIM-1）表达的影响。方法96只雄性sD大鼠随机分为假手术组、模型组、低剂量治疗组及高剂量治疗组，每组24只。模型组和治疗组采用左侧输尿管结扎术造成UUO，假手术组仅游离左侧输尿管而不结扎，术后立即分别予低、高剂量治疗组大鼠腹腔注射硫氢化钠1．4、7．0μmol／kg，每日2次；假手术组、模型组则予腹腔注射等量9g／L盐水。各组分别于建模后第7、14、21天分批处死动物8只，采用去蛋白法测定血浆H2s水平。HE染色评定肾小管间质病理指数评分，Masson染色测定。肾间质纤维化相对面积。免疫组织化学法检测ED-1、KIM-1表达。结果1．病理结果提示假手术组肾小管间质变化不明显。模型组和治疗组肾小管上皮细胞肿胀、空泡变性，管腔扩张，。肾间质增宽，间质细胞和细胞外基质成分增多。模型组和治疗组各时间点。肾小管间质病理损伤明显高于假手术组（P〈0．05），高、低剂量治疗组肾小管问质病理损伤明显低于模型组（P〈0．05），但低、高剂量治疗组间比较差异无统计学意义（P〉0．05）。2．免疫组织化学分析显示模型组和治疗组各时间点肾小管问质ED-1、KIM-l表达明显高于假手术组（P〈0．05），治疗组肾小管问质ED-1、KIM-1表达明显低于模型组（P〈0．05），但低、高剂量治疗组间比较差异无统计学意义（P〉0．05）。3．模型组和治疗组各时间点血浆H：s水平低于假手术组（P〈0．05）。高、低剂量治疗组血浆H：s水平明显高于模型组（P〈0．05），但低、高剂量治疗组间比较差异无统计学意义（P〉0．05）。结论H：s可能部分通过减少肾小管间质ED-1和KIM-1的表达而达到减轻。肾间质纤维化的肾保护作用。
Objective To investigate the effects of hydrogen sulfide （H2 S） on the tubular interstitial fibrosis and on the levels of kidney injury molecule-1 （ KIM-1 ） and ectodermal dysplasia-1 （ ED-1 ） in the process of renal inter- stitial fibrosis in rats with unilateral ureteral occlusion （ UUO ）. Methods Ninety-six Sprague-Dauley （SD） male rats were divided into 4 groups randomly ： sham-operated group （ n = 24 ） , model group （ n = 24 ） , low-dose therapy group （ n = 24 ） and high-dose therapy group （ n = 24）. The rats in the model group and treatment groups were ligated at the left u- reter and UUO was induced, meanwhile, the rats in the control group were free from the left ureter ligation. Rats received sodium hydrosulfide （NariS） in traperitoneatly（ 1.4 p, mol/kg, twice a day） , and NariS （7.0 ~mol/kg, twice a day） , re- spectively. Rats in sham-operated group and the model group were injected intraperitoneally with identical voluminal 9 g/L saline. Eight rats in each group were sacrificed randomly at the 7 days, 14 days and 21 days,respectively. The concentration of plasma H2 S was detected. Renal tubular interstitial damage and interstitial fibrosis were evaluated with routine HE staining and Masson staining under microscope, and both of them were used to evaluate the obstruction of re- nal histopathological changes. The expressions of ED-1 and KIM-1 were measured with immunohistoehemical staining. Results 1. The pathological findings showed that the renal tubular interstitial changes were not obvious in the sham- operated group. The tubular epithelial cells in the model group and treatment groups showed swelling and vacuoles de- generation, with renal interstitial broadening, interstitial ceils and extraeellular matrix increasing. The renal tubular inter- stitial pathological injury of model group and treatment group were more serious than those in the sham-operated group at each time point（P 〈0.05）. The renal tubular interstitial pathological injury of the treatment groups were obviously lower than that in the model group（ P 〈 0.05 ）. However, there was no statistically significant difference between high- dose therapy group and low-dose therapy group（ P 〉 0.05 ）. 2. Immunohistochemical analysis showed that expressions of ED-I and KIM-1 in renal tubular interstitices in the model group and the treatment groups were higher than those in the sham-operated group at each time point（ P 〈 0.05 ）. The expressions of ED-1 and KIM-1 in renal tubular interstitiees in the treatment groups were obviously lower than those in the model group（ P 〈 0.05 ）. There was no statistically signifi-cant difference between the high-dose therapy group and the low-dose therapy group（ P 〉 0.05 ）. 3. Plasma H2S levels in model group and treatment group were lower than those in the sham-operated group at each time point（ P 〈 0.05）. The plasma H2 S level of the treatment group was obviously higher than that in the model group （ P 〈 0.05 ）. However, there was no statistically significant difference between high-dose therapy group and low-dose therapy group （ P 〉 0. 05）. Conclusions H2S implements renal protection effect partly by reducing the expression of ED-1 and KIM-1 in tubule interstitices to ease tubular interstitial fibrosis.
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2013年第23期1812-1816,共5页
Chinese Journal of Applied Clinical Pediatrics
基金
新乡医学院第七批省级重点学科开放课题（ZD2009-12）
