目的 探讨水苏碱对单侧输尿管梗阻大鼠肾组织蛋白激酶R样内质网激酶（PERK）表达的影响。方法 建立单侧输尿管梗阻诱导大鼠肾间质纤维化的动物模型；将大鼠随机分为假手术组，模型组，依那普利组，水苏碱高、中、低剂量组；于术后第14天处死大鼠收集血清测定血肌酐（Scr）、尿素氮（BUN）；采用HE染色观察肾脏的病理改变及评定肾小管损伤指数；Masson染色观察肾间质胶原沉积的面积，判断肾间质纤维化程度；采用免疫组织化学方法检测肾组织中PERK、激活转录因子4（ATF4）、C/EBP 同源蛋白（CHOP）的表达。结果 各治疗组与模型组比较，BUN、Scr均明显降低，肾小管损伤程度明显减轻，肾间质胶原相对面积和PERK、ATF4、CHOP的表达显著降低（P<0.05、0.01）。与依那普利组比较，水苏碱高剂量组的抗肾间质纤维化作用更为显著（P<0.05）。结论 水苏碱能够抑制PERK信号通路介导ATF4蛋白表达水平升高及ATF4激活CHOP的蛋白表达，阻止细胞凋亡，从而减缓了肾间质纤维化的发生和发展。

Objective To investigate the effect of stachydrine on the expression of protein kinase R-like endoplasmic reticulum kinase (PERK) in renal tissue of rats with unilateral ureteral obstruction (UUO). Methods To establish the animal model of renal interstitial fibrosis induced by UUO. The rats were randomly divided into the Sham, model Enalapril, high-, mid-, and low-dose stachydrine groups. Rats were sacrificed to collect serum for determining the serum creatinine (Scr) and blood urea nitrogen (BUN) after day 14 of surgery. HE staining was used for observation of kidney pathological changes and the assessment of renal tubular damage indexes. Masson staining was applied to the semi-quantitative analysis of relative area of renal interstitial fibrosis (RIF) and degree of RIF. The expression of PERK, activiting transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) was detected by immunohistochemical methods. Results Compared with the model group, the levels of Bun, Scr, the tubular injury, the relative area of renal interstitial collagen, and the expression of PERK, ATF4, and CHOP was significantly reduced in the treatment groups (P <0.05, 0.01). The high stachydrine was more effective than Enalapril in inhibiting RIF (P <0.05). Conclusion The stachydrine could inhibit the increasing expressions of ATF4 induced by PERK signaling pathway and CHOP activated by ATF4. The apoptosis are blocked to slow down the occurrence and development of RIF.

国家自然科学基金资助项目（81373547）；黑龙江省自然科学基金项目（D201147）；黑龙江省教育厅基金项目（11531451）