昆布多糖对肾纤维化大鼠肾组织内质网应激的保护作用

目的研究昆布多糖对肾纤维化大鼠肾组织内质网应激(ERS)分子伴侣GRP78、GRP94蛋白表达的影响。方法采用单侧输尿管梗阻(UUO)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、昆布多糖高、中、低剂量组。术后第7天处死大鼠,收集血清测定肌酐(Scr)、尿素氮(BUN)水平。采用Western免疫印迹法检测大鼠肾组织GRP78、GRP94的蛋白表达;采用HE、Masson染色检测肾小管损伤及肾间质纤维化程度。结果各治疗组与模型组比较大鼠肾小管间质损伤指数、肾间质纤维化程度、血清Scr、BUN水平及肾组织GRP78、GRP94蛋白表达有差异(P<0.05;P<0.01),昆布多糖与依那普利组比较,大鼠肾组织GRP78、GRP94表达升高(P<0.05),肾小管间质损伤及肾间质纤维化程度明显降低(P<0.05),肾功能Scr、BUN明显降低(P<0.05)。结论UUO早期昆布多糖可能通过上调ERS分子伴侣GRP78、GRP94蛋白表达,协助变性蛋白进行重新折叠、装配及跨膜转运,抑制未折叠蛋白反应,阻断ERS应激信号传导通路,从而减轻肾间质纤维化的发生和发展。

Protection of kelp polysaccharides on endoplasmic reticulum stress of rats with renal interstitial fibrosis

Objective To observe the effects of kelp polysaccharides on endoplasmic reticulum stress of renal fibrosis rats kidney tissues and the expressions of chaperone GRP78,GRP94.Methods Unilateral ureter obstruction(UUO) was used to induce rats renal intersitital fibrosis animal models.The rats were randomly divided into 6 groups,including sham operation group,model group,enalaprilat group,kelp polysaccharides high,midium and low-dosage groups.Seven days after operation,the rats were executed and the levels of serum creatinine and urea nitrogen were determined.The expressions of rats kidney tissue GRP78,GRP94 through Western Blot,HE,Masson dyeing method for the damage of tublars and renal fibrosis degree were detected after UUO.Results The tubulointerstitium damage index,renal fibrosis degrees,the levels of serum creatinine and urea nitrogen and expressions of chaperone GRP78,GRP94 differed between treatment groups and model groups(P<0.05;P<0.01).Compared with enalaprilat group,expressions of chaperone GRP78,GRP94 improved(P<0.05) in kelp polysaccharide group,the tubulointerstitium damage and renal fibrosis degree remarkably decreased(P<0.05),serum creatinine and urea nitrogen reduced as well(P<0.05).Conclusion Kelp polysaccharides may increase the expressions of chaperone GRP78,GRP94 and help degeneration proteins with refolding,assembly,transition,subsequently supress unfolding proteins;block the endoplasmic reticulum stress signal pathway to attentuate the development of renal intersitital fibrosis.