全球慢性肾脏病的发生率近年来逐年上升，核心病理改变是肾间质纤维化（RIF）。前期我们已对内质网应激( ERS)下游网络信号传导通路进行了研究，表明该法能抑制肾纤维化大鼠细胞凋亡。本课题在国内外首次引用温补脾肾泄浊化瘀依法拆方干预肾纤维化ERS激活CHOP逆转可控性研究，采用Western法从体内检测各实验组GRP78、GRP94、ORP150、PERK、elF2a、ATF4、CHOP蛋白表达水平。采用HE、PASM、Masson染色法评估肾小管损害和肾间质纤维化的程度，TUNEL法观察肾小管上皮细胞凋亡情况；以阐明ERS激活CHOP转录在RIF中的作用机制及温补脾肾泄浊化瘀依法拆方的干预作用及复方配伍规律，为RIF的逆转找到新的可靠的治疗靶点。

The global Chronic Kidney Disease(CKD) increases by years. Nuclear pathological change is Renal Interstitial Fibrosis(RIF). We early studied the downstream network signaling pathway of endoplasmic reticulum stress (ERS). It indicated that our method could inhibit the apoptosis in rat with renal fibrosis. Our subject is the first to interfere in the renal fibrosis ERS activating CHOP with the decomposed recipes of Wenbu Pishen, Xiezhuo Huayu according to the formula. Western Blot are used in vivo to detect the protein expressions of molecular chaperone GRP78, GRP94, ORP150, PERK, eIF2α, ATF4, CHOP. Vivo experiment: HE, PASM, Masson staining for valuing the tubular damage and the degree of RIF; TUNEL for the apoptosis of renal tubular epithelial cells. The mechanism of ERS activating transcription of CHOP in RIF will be clarified. The interference of decomposed recipes of Wenbu Pishen, Xiezhuo Huayu according to the formula in RIF and its compound compatibility law will be illustrated. Also, the new reliable treatment target for reversing RIF will be found.

目的：对温补脾肾泄浊化瘀依法拆方干预肾纤维化ERS激活CHOP逆转可控性进行研究。方法：采用单侧输尿管梗阻建立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、温补脾肾泄浊化瘀组、温补脾肾组、泄浊化瘀组。分别于造模后第7天、第14天处死大鼠，收集大鼠血清测定肌酐(Cre)、尿素氮(Ure)；摘取左侧肾脏，称量肾脏重量比较分析，观察肾脏水肿程度；采用HE、Masson染色观察肾脏的病理改变并且评定肾小管损伤指数，判断肾间质纤维化程度；采用Western Blot免疫印迹法检测各实验组内质网分子伴侣GRP78、GRP94、GRP150、PERK、EIF2α、ATF4、CHOP蛋白表达水平；采用TUNEL法测定肾小管上皮细胞的凋亡指数。结果：①血清Cre、Ure水平：7天温补脾肾泄浊化瘀法与依那普利组比较Cre水平有显著性差异(P<0.05)；14天温补脾肾泄浊化瘀法与依那普利组比较，降低Cre、Ure作用明显(P<0.05)；②肾重变化：术后第7、14天温补脾肾泄浊化瘀法与依那普利组比较更能减轻肾重(P<0.05)；③肾小管损伤指数：术后第7、14天，温补脾肾泄浊化瘀法与依那普利组比较，肾小管损伤指数有差异(P<0.05)；④肾间质纤维化程度：术后第7、14天，温补脾肾泄浊化瘀法与依那普利组比较，减少肾间质胶原相对面积的效果显著（P<0.05）；⑤ERS分子伴侣：术后14天，各治疗组与模型组和依那普利组比较均能不同程度的降低GRP78、GRP94、PERK、EIF2α、ATF4、CHOP蛋白的表达，升高GRP150的表达。⑥肾小管上皮细胞凋亡情况：7天和14天温补脾肾泄浊化瘀法与依那普利组比较，凋亡细胞指数明显降低（P<0.05）。结论：温补脾肾泄浊化瘀法及其拆方能够不同程度保护单侧输尿管梗阻大鼠的肾功能，干扰内质网应激过程介导的细胞凋亡通路，阻碍细胞凋亡沉积引起的肾间质纤维化。