CAJ | 학술논문

目的：探讨内质网应激（ endoplasmic reticulum stress， ERS）及相关炎症反应在糖尿病大鼠肾脏损害中的作用及血管紧张素II受体拮抗剂缬沙坦对其的影响。方法采用腹腔注射链脲佐菌素方法建立糖尿病肾病大鼠模型。将大鼠随机分为对照组（ Con组）、糖尿病组（ DM组）、缬沙坦组（ DM＋V组）。缬沙坦组每日灌胃给予缬沙坦（10 mg／kg）共6周。应用免疫组化法及Western blot方法检测ERS相关蛋白P-IRE1α、P-JNK及中性粒细胞趋化因子MCP-1的表达及定位，实时荧光定量PCR（ FQ-PCR）检测IRE1α、JNK及MCP-1mRNA的表达变化，同时观察各组大鼠尿蛋白、BUN、Scr等指标的变化。结果与Con组相比，DM组大鼠肾脏病理炎细胞浸润加重，P-IRE1α、IRE1α、P-JNK、MCP-1蛋白表达上调，IRE1αmRNA、MCP-1mRNA表达水平上调；与DM组相比，DM＋V组肾脏病理炎症细胞浸润减轻，P-IRE1α、IRE1α、P-JNK、MCP-1蛋白表达下调，IRE1αmRNA、MCP-1 mRNA表达水平下调。3组间JNK mRNA及蛋白表达无明显差异。结论糖尿病大鼠肾脏中存在内质网应激和炎症反应的激活，缬沙坦可能部分通过抑制内质网应激中的IRE1／JNK／MCP-1通路，减少炎症反应，从而发挥肾脏保护作用。
목적：탐토내질망응격（ endoplasmic reticulum stress， ERS）급상관염증반응재당뇨병대서신장손해중적작용급혈관긴장소II수체길항제힐사탄대기적영향。방법채용복강주사련뇨좌균소방법건립당뇨병신병대서모형。장대서수궤분위대조조（ Con조）、당뇨병조（ DM조）、힐사탄조（ DM＋V조）。힐사탄조매일관위급여힐사탄（10 mg／kg）공6주。응용면역조화법급Western blot방법검측ERS상관단백P-IRE1α、P-JNK급중성립세포추화인자MCP-1적표체급정위，실시형광정량PCR（ FQ-PCR）검측IRE1α、JNK급MCP-1mRNA적표체변화，동시관찰각조대서뇨단백、BUN、Scr등지표적변화。결과여Con조상비，DM조대서신장병리염세포침윤가중，P-IRE1α、IRE1α、P-JNK、MCP-1단백표체상조，IRE1αmRNA、MCP-1mRNA표체수평상조；여DM조상비，DM＋V조신장병리염증세포침윤감경，P-IRE1α、IRE1α、P-JNK、MCP-1단백표체하조，IRE1αmRNA、MCP-1 mRNA표체수평하조。3조간JNK mRNA급단백표체무명현차이。결론당뇨병대서신장중존재내질망응격화염증반응적격활，힐사탄가능부분통과억제내질망응격중적IRE1／JNK／MCP-1통로，감소염증반응，종이발휘신장보호작용。
Objective To study the role of endoplasmic reticulum stress and related inflammation in the kidneys of rats with diabetic nephropathy and the effect of valsartan on these lesions.Methods The diabetic rat model was induced by intraperitoneal injection of streptozotocin.Thirty-four healthy male SD rats were randomly divided into normal control group (n=10), diabetic group (n=12), and valsartan group (n=12).Valsartan (10 mg/kg) was administered daily by gavage from the next day of the diabetes induction for 6 weeks.The expression and distribution of ERS-related proteins P-IRE1α, P-JNK, and MCP-1 were examined by immunohistochemistry and Western blot.Real-time fluorescence quantita-tive PCR was used to detect the mRNA expressions of IRE1α, JNK and MCP-1.The 24-hour urine protein excretion, Scr, and BUN were checked.Results Compared with the control group, infiltration of inflammatory cells was aggravated in the kidneys of DM+V group, the expressions of P-IRE1α,IRE1α,P-JNK,MCP-1 were significantly increased, and the levels of IRE1mRNA and MCP-1mRNA increased compared with the DM group, infiltration of inflammation cells was alleviated in the kidney of DM+V group, the protein expressions of P-IRE1α,IRE1α,P-JNK,MCP-1 were significantly reduced, the levels of IRE1mRNA and MCP-1mRNA were reduced.While there was no significant difference in the expression of JNK mRNA and protions among the three groups.Conclusions ERS and related inflammation are activated in the kidney of di-abetic rats.Inhibition of the IRE1/JNK/MCP-1 pathway of ERS and related inflammation might be responsible for the pro-tective effects of valsartan on the kidneys of diabetic rats.