中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
4期
532-536,537
,共6页
严国强%陈春香%陈芳辉%高艳%储佳佳%李腾%黄起壬
嚴國彊%陳春香%陳芳輝%高豔%儲佳佳%李騰%黃起壬
엄국강%진춘향%진방휘%고염%저가가%리등%황기임
卡托普利%高糖%人脐静脉内皮细胞%胰岛素抵抗%PPARγ%NO%ET-1
卡託普利%高糖%人臍靜脈內皮細胞%胰島素牴抗%PPARγ%NO%ET-1
잡탁보리%고당%인제정맥내피세포%이도소저항%PPARγ%NO%ET-1
captopril%high glucose%human umbilical vein endothelium cells%insulin resistance%PPARγ%NO%ET-1
目的:研究卡托普利(captopril,Cap)对高糖(high glu-cose,HG,33 mmol·L -1)诱导的人脐静脉内皮细胞(human umbilical vein endothelium cells,HUVECs)胰岛素抵抗(insulin resistance,IR)的作用及机制。方法首先观察 Cap 对 HG (33 mmol·L -1)诱导的 HUVECs IR 的改善作用。实验随机分为5组,即正常对照(Control)组、IR 组、IR +CapⅠ(1×10-6 mol·L -1)组、IR +CapⅡ(1×10-5 mol·L -1)组、IR +CapⅢ(1×10-4 mol·L -1)组。其次证实 Cap 改善 HG(33 mmol·L -1)诱导 HUVECs IR 的作用是由 PPARγ介导。实验随机分为6组,即 Control 组、IR 组、IR +Cap(1×10-5 mol ·L -1)组、PPARγ抑制剂 GW9662(PI,1.0μmol·L -1)组、IR +PPARγ抑制剂(IR +PI,1.0μmol·L -1)组、IR +Cap +PPARγ抑制剂(IR +Cap +PI,1.0μmol·L -1)组,除 Control组和 PI 组外,所有各组先用含33 mmol · L -1葡萄糖的DMEM培养48 h,Cap 各组再加不同浓度的 Cap 处理4 h,最后胰岛素(100 nmol·L -1)处理30 min,抑制剂组再加抑制剂(1.0μmol·L -1)处理1 h,最后进行指标检测。结果IR组 NO 水平明显降低、ET-1含量明显升高,提示细胞已产生IR,但 PPARγmRNA 和蛋白表达水平与 Control 组相比差异无统计学意义(P >0.05);Cap 呈浓度依赖性逆转 HG 诱导NO 和 ET-1水平的改变,明显增加磷酸化 PPARγ(P-PPARγ)水平,说明其可明显改善 HG 诱导的 IR,但对PPARγmRNA 和蛋白表达水平无明显影响(vs IR,P >0.05);加 PI 处理后,Cap 改善 IR 的作用完全取消,提示 Cap改善 IR 的作用是由 PPARγ介导。结论 Cap 可通过PPARγ介导改善高糖所致血管内皮细胞 IR,其机制可能与PPARγ表达水平无关,而与 PPARγ激活有关。
目的:研究卡託普利(captopril,Cap)對高糖(high glu-cose,HG,33 mmol·L -1)誘導的人臍靜脈內皮細胞(human umbilical vein endothelium cells,HUVECs)胰島素牴抗(insulin resistance,IR)的作用及機製。方法首先觀察 Cap 對 HG (33 mmol·L -1)誘導的 HUVECs IR 的改善作用。實驗隨機分為5組,即正常對照(Control)組、IR 組、IR +CapⅠ(1×10-6 mol·L -1)組、IR +CapⅡ(1×10-5 mol·L -1)組、IR +CapⅢ(1×10-4 mol·L -1)組。其次證實 Cap 改善 HG(33 mmol·L -1)誘導 HUVECs IR 的作用是由 PPARγ介導。實驗隨機分為6組,即 Control 組、IR 組、IR +Cap(1×10-5 mol ·L -1)組、PPARγ抑製劑 GW9662(PI,1.0μmol·L -1)組、IR +PPARγ抑製劑(IR +PI,1.0μmol·L -1)組、IR +Cap +PPARγ抑製劑(IR +Cap +PI,1.0μmol·L -1)組,除 Control組和 PI 組外,所有各組先用含33 mmol · L -1葡萄糖的DMEM培養48 h,Cap 各組再加不同濃度的 Cap 處理4 h,最後胰島素(100 nmol·L -1)處理30 min,抑製劑組再加抑製劑(1.0μmol·L -1)處理1 h,最後進行指標檢測。結果IR組 NO 水平明顯降低、ET-1含量明顯升高,提示細胞已產生IR,但 PPARγmRNA 和蛋白錶達水平與 Control 組相比差異無統計學意義(P >0.05);Cap 呈濃度依賴性逆轉 HG 誘導NO 和 ET-1水平的改變,明顯增加燐痠化 PPARγ(P-PPARγ)水平,說明其可明顯改善 HG 誘導的 IR,但對PPARγmRNA 和蛋白錶達水平無明顯影響(vs IR,P >0.05);加 PI 處理後,Cap 改善 IR 的作用完全取消,提示 Cap改善 IR 的作用是由 PPARγ介導。結論 Cap 可通過PPARγ介導改善高糖所緻血管內皮細胞 IR,其機製可能與PPARγ錶達水平無關,而與 PPARγ激活有關。
목적:연구잡탁보리(captopril,Cap)대고당(high glu-cose,HG,33 mmol·L -1)유도적인제정맥내피세포(human umbilical vein endothelium cells,HUVECs)이도소저항(insulin resistance,IR)적작용급궤제。방법수선관찰 Cap 대 HG (33 mmol·L -1)유도적 HUVECs IR 적개선작용。실험수궤분위5조,즉정상대조(Control)조、IR 조、IR +CapⅠ(1×10-6 mol·L -1)조、IR +CapⅡ(1×10-5 mol·L -1)조、IR +CapⅢ(1×10-4 mol·L -1)조。기차증실 Cap 개선 HG(33 mmol·L -1)유도 HUVECs IR 적작용시유 PPARγ개도。실험수궤분위6조,즉 Control 조、IR 조、IR +Cap(1×10-5 mol ·L -1)조、PPARγ억제제 GW9662(PI,1.0μmol·L -1)조、IR +PPARγ억제제(IR +PI,1.0μmol·L -1)조、IR +Cap +PPARγ억제제(IR +Cap +PI,1.0μmol·L -1)조,제 Control조화 PI 조외,소유각조선용함33 mmol · L -1포도당적DMEM배양48 h,Cap 각조재가불동농도적 Cap 처리4 h,최후이도소(100 nmol·L -1)처리30 min,억제제조재가억제제(1.0μmol·L -1)처리1 h,최후진행지표검측。결과IR조 NO 수평명현강저、ET-1함량명현승고,제시세포이산생IR,단 PPARγmRNA 화단백표체수평여 Control 조상비차이무통계학의의(P >0.05);Cap 정농도의뢰성역전 HG 유도NO 화 ET-1수평적개변,명현증가린산화 PPARγ(P-PPARγ)수평,설명기가명현개선 HG 유도적 IR,단대PPARγmRNA 화단백표체수평무명현영향(vs IR,P >0.05);가 PI 처리후,Cap 개선 IR 적작용완전취소,제시 Cap개선 IR 적작용시유 PPARγ개도。결론 Cap 가통과PPARγ개도개선고당소치혈관내피세포 IR,기궤제가능여PPARγ표체수평무관,이여 PPARγ격활유관。
Aim To investigate the role of captopril in insulin resistance of endothelial cells induced by high glucose.Methods 1 .Improvement effect of captopril on insulin resistance in HUVECs was observed.The HUVECs were seeded in a 6-well plate and were ran-domly divided into 5 groups,namely,control group, IR group,IR together with different Cap concentrations (low,medium and high concentration),respectively. 2.Improvement effect of Cap on insulin resistance was mediated by PPARγin HUVECs.HUVECs were ran-domly divided into 6 groups,namely,control group, control +PPARγinhibitor (PI)(1 .0 μmol · L -1 ) group,IR group,IR +PI(1 .0 μmol·L -1 )group,IR +Cap(1 ×1 0 -5 mol·L -1 ) group,and IR +Cap +PI (1 .0 μmol·L -1 )group.All indicators were detected. Results After HUVECs were incubated with media containing 33 mmol·L -1 of glucose for 48 h,the NO levels were significantly decreased while ET-1 levels were significantly elevated,showing a significant differ-ence between IR group and control group (P <0.01 ). The expression levels of PPARγmRNA and its protein were somewhat up-regulated,but there was no signifi-cant difference between IR group and control group (P>0.05).When the HUVECs in IR group were treated with DMEM containing glucose (33 mmol·L -1 )for 48 h and insulin for 30 min,the expression levels of PPARγmRNA and its protein in Cap groups were simi-lar to those in the IR group,and there was no signifi-cant difference between the two groups (P >0.05 );however, the expression levels of phosphorylated PPARγprotein in Cap groups were increased compared with IR group (P <0.05).The levels of NO were sig-nificantly increased whereas the levels of ET-1 were decreased in Cap groups,which had significant differ-ences compared with IR group (P <0.05).Nonethe-less,pre-treating with GW9662,a PPARγinhibitor, the improvement effects of Cap were markedly abol-ished.Conclusions Captopril could improve high glucose-induced insulin resistance of endothelial cells mediated by PPARγ,and the underlying mechanisms are related to the activation of PPARγ,rather than its expression.