目的:探讨过氧化物酶体增殖物激活受体γ(RRAR-γ)激动剂罗格列酮干预Toll样受体4/磷脂酰肌醇3-激酶(TLR4/PI3K)信号通路对脂多糖(LPS)诱导人冠状动脉血管内皮细胞(HCAEC)缝隙连接蛋白43(Cx43)表达的影响。方法:用LPS诱导建立HCAEC炎症...目的:探讨过氧化物酶体增殖物激活受体γ(RRAR-γ)激动剂罗格列酮干预Toll样受体4/磷脂酰肌醇3-激酶(TLR4/PI3K)信号通路对脂多糖(LPS)诱导人冠状动脉血管内皮细胞(HCAEC)缝隙连接蛋白43(Cx43)表达的影响。方法:用LPS诱导建立HCAEC炎症模型,将细胞分为模型组、TLR4激动剂KLA组、PI3K抑制剂LY294002组、罗格列酮组、KLA+罗格列酮组、LY294002+罗格列酮组,另设空白组(不作任何处理)。分别采用实时荧光定量PCR(qPCR)、Western blotting法检测细胞中Cx43、TLR4、PI3K m RNA和蛋白表达。结果:KLA+罗格列酮组TLR4表达明显低于KLA组(P<0.05)。LY294002+罗格列酮组PI3K表达明显低于LY294002组(P<0.05)。模型组Cx43表达明显低于空白组(P<0.05),KLA+罗格列酮组Cx43表达明显高于KLA组(P<0.05),LY294002+罗格列酮组Cx43表达明显高于LY294002组(P<0.05)。结论:PPAR-γ激动剂罗格列酮可抑制TLR4/PI3K信号通路并上调HCAEC中Cx43的表达。展开更多
Objectives To investigate the effects of nicotine on angiogenesis and restenosis in a rabbit model of critical limb ischemia and balloon catheter denuding injury iliac artery. Methods Forty male New Zealand White rabb...Objectives To investigate the effects of nicotine on angiogenesis and restenosis in a rabbit model of critical limb ischemia and balloon catheter denuding injury iliac artery. Methods Forty male New Zealand White rabbits were randomly divided into control, low-, middle-, and high-dose (0.005, 0.05 or 5 μg/kg, respectively) nicotine groups. Balloon catheter denuding injury iliac artery and ligation of a femoral artery were performed in all animals fed with a high-cholesterol diet (HCD) beginning 2 weeks before operation. Nicotine was administered daily by intramuscular injection in the ischemic hindlimb for 3 weeks. Control rabbits received an equal volume of phosphate-buffered saline alone. Collateral vessels of the ischemic hindlimb were observed by angiography of abdominal aorta, and the density of intramuscular microvessels in ischemic hindlimb was examined by immunohistochemistry. The levels of blood lipids and the indexes of hepatic or renal functions were also determined before HCD and after nicotine treatment. Results One rabbit in control, two in low-, one in middle- and two in high-dose group died during the experiment. The remaining 34 rabbits were included in the study. Two or five weeks after HCD, the levels of blood lipids were significantly increased in all groups, but there was no significant difference on the levels between control and nicotine-treated groups three weeks after nicotine treatment; The indexes of hepatic or renal functions were no significant changes three weeks after nicotine treatment; There were no significant differences on collateral vessels shown by angiography in all four groups; The density of intramuscular microvessels in three nicotine -treated groups was significantly higher than that in control group; But the intimal area in all three nicotine-treated groups was also larger than that in control group. Conclusions The present study shows that intramu- scular administration of nicotine for three weeks could not increase arteriogenesis in ischemic hindlimb of rabbits, but is capable of significantly promoting intramuscular angiogenesis in ischemic hindlimb. Nicotine can also accelerate intimal thickening of balloon catheter denuding injury iliac artery, so it may contribute to the development of restenosis.展开更多
文摘目的:探讨过氧化物酶体增殖物激活受体γ(RRAR-γ)激动剂罗格列酮干预Toll样受体4/磷脂酰肌醇3-激酶(TLR4/PI3K)信号通路对脂多糖(LPS)诱导人冠状动脉血管内皮细胞(HCAEC)缝隙连接蛋白43(Cx43)表达的影响。方法:用LPS诱导建立HCAEC炎症模型,将细胞分为模型组、TLR4激动剂KLA组、PI3K抑制剂LY294002组、罗格列酮组、KLA+罗格列酮组、LY294002+罗格列酮组,另设空白组(不作任何处理)。分别采用实时荧光定量PCR(qPCR)、Western blotting法检测细胞中Cx43、TLR4、PI3K m RNA和蛋白表达。结果:KLA+罗格列酮组TLR4表达明显低于KLA组(P<0.05)。LY294002+罗格列酮组PI3K表达明显低于LY294002组(P<0.05)。模型组Cx43表达明显低于空白组(P<0.05),KLA+罗格列酮组Cx43表达明显高于KLA组(P<0.05),LY294002+罗格列酮组Cx43表达明显高于LY294002组(P<0.05)。结论:PPAR-γ激动剂罗格列酮可抑制TLR4/PI3K信号通路并上调HCAEC中Cx43的表达。
基金This work was supported by the special grants of "NewCentury Ten-Hundred-Thousand Talent Engineering"ofGuangxi, China (Project No.: 2001212) and by the researchgrants of Guangxi Natural Science Foundation, China(Guikeji: 0342009-2)
文摘Objectives To investigate the effects of nicotine on angiogenesis and restenosis in a rabbit model of critical limb ischemia and balloon catheter denuding injury iliac artery. Methods Forty male New Zealand White rabbits were randomly divided into control, low-, middle-, and high-dose (0.005, 0.05 or 5 μg/kg, respectively) nicotine groups. Balloon catheter denuding injury iliac artery and ligation of a femoral artery were performed in all animals fed with a high-cholesterol diet (HCD) beginning 2 weeks before operation. Nicotine was administered daily by intramuscular injection in the ischemic hindlimb for 3 weeks. Control rabbits received an equal volume of phosphate-buffered saline alone. Collateral vessels of the ischemic hindlimb were observed by angiography of abdominal aorta, and the density of intramuscular microvessels in ischemic hindlimb was examined by immunohistochemistry. The levels of blood lipids and the indexes of hepatic or renal functions were also determined before HCD and after nicotine treatment. Results One rabbit in control, two in low-, one in middle- and two in high-dose group died during the experiment. The remaining 34 rabbits were included in the study. Two or five weeks after HCD, the levels of blood lipids were significantly increased in all groups, but there was no significant difference on the levels between control and nicotine-treated groups three weeks after nicotine treatment; The indexes of hepatic or renal functions were no significant changes three weeks after nicotine treatment; There were no significant differences on collateral vessels shown by angiography in all four groups; The density of intramuscular microvessels in three nicotine -treated groups was significantly higher than that in control group; But the intimal area in all three nicotine-treated groups was also larger than that in control group. Conclusions The present study shows that intramu- scular administration of nicotine for three weeks could not increase arteriogenesis in ischemic hindlimb of rabbits, but is capable of significantly promoting intramuscular angiogenesis in ischemic hindlimb. Nicotine can also accelerate intimal thickening of balloon catheter denuding injury iliac artery, so it may contribute to the development of restenosis.
