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作 者:尤莉[1] 陆福明[1] 杨海春[1] 林善锬[1]
机构地区:[1]复旦大学附属华山医院肾内科,上海200040
出 处:《复旦学报(医学版)》2002年第6期433-436,共4页Fudan University Journal of Medical Sciences
摘 要:目的 研究血管紧张素Ⅱ (ANGⅡ )、高糖及血管紧张素Ⅱ 1型受体拮抗剂 (AT1RA)对于大鼠系膜细胞 (MCs)上葡萄糖转运蛋白 1(GLUT1)表达及MCs所合成的系膜区细胞外基质 (ECM )的影响。方法 采用免疫组化法检测大鼠系膜细胞上GLUT1蛋白的合成 ,半定量聚合酶链式反应 (RT PCR)测定系膜细胞GLUTmR NA水平 ,ELISA法测定细胞培养上清液中纤连蛋白 (FN)的表达。结果 ANGⅡ作用后能显著增加大鼠MCs GLUT1的转录及蛋白合成 (P <0 .0 5 ) ,这种作用具有浓度及时间依赖性且能被AT1RA伊贝沙坦 (Irbesartan)所阻断。高糖 (2 7.8mm1/L)作用 4h后未能增加MCsGLUT1的转录及表达。ANGⅡ能使培养的MCs上清液中FN含量显著增加 (P <0 .0 0 1) ,Irbesartan能使增加的FN降低 5 0 .5 4%。结论 ANGⅡ能从转录水平刺激MCs上GLUT1的表达 ,增加ECM的合成 ,ANGⅡ的这种作用通过AT1受体介导并能被AT1RA阻断。ANGⅡ可通过上调GLUT1的表达参与糖尿病肾病 (DN)的发生及发展。Purpose To investigate effects of angiotensin Ⅱ(ANG Ⅱ),hyperglycemia and AT?1 receptor antagonist on the expression of glucose transporter-1(GLUT?1) and extracellular matrix(ECM)formation in cultured rat mesangial cells(MCs). Methods We detected the GLUT1 protein expression of MCs with immunohistochemistry,determined the GLUT1 mRNA level with quantitative reverse transcription polymerase chain reaction (RT?PCR).An enzyme-linked immunohistochemistry assay(ELISA)was used to determine the content of the fibronectin (FN)in the supernate. Results MCs incubated with ANG Ⅱ demonstrated significantly increase in GLUT?1 transcription and protein expression(P<0.05).This effect of ANG Ⅱ was time and concentration dependent and could be blocked by AT?1 receptor antagonist,irbesartan.High glucose concentration(27.8 mmlo/L)had no effects on the expression of GLUT?1 in our study of 4 hours.MCs exposed to ANG Ⅱalso demonstrated increase in supernate FN content(P<0.001).Irbesartan abbreviated high of supernate FN by decreasing its content of 50.54%. Conclusions ANG Ⅱ can stimulate the MCs expression of GLUT1 on transcribe level and increase the production of ECM.This effect is mediated by angiotensinⅡtype 1 receptor and can be blocked by irbesartan.ANG Ⅱ may participate in the pathogenesis and the progression of diabetic nephropthy(DN)by upregulating the expression of GLUT1.
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