目的：研究白细胞介素-1β经血管外膜给药导致动脉平滑肌细胞发生的改变及其与JAK2-STAT3信号通路的关系，明确JAK2-STAT3信号通路在血管增殖性病变中的作用。

目的 研究白细胞介素-1β经血管外膜给药导致动脉平滑肌细胞发生的改变及其与JAK2-STAT3信号通路的关系,明确JAK2-STAT3信号通路在血管增殖性病变中的作用.方法 6～8周龄SD雄性大鼠24只,分离左侧颈总动脉,实验组(n=18)血管外膜包裹含白介素-1β2.5μg的琼脂缓释悬液,对照组(n=6)包裹不含白介素的琼脂悬液,术后2、8、24、48 h,1、2周分别处死实验组大鼠3只,对照组1只,血管标本经切片HE染色观察形态,Westernblot法检测JAK2、STAT3、磷酸化JAK2以及磷酸化STAT3的表达,免疫组化标记定位磷酸化JAK2及磷酸化STAT3；另取SD雄性大鼠9只,分离两侧颈总动脉,左侧滴加JAK2抑制剂AG490缓释凝胶,右侧滴加等量空白凝胶后两侧均包裹等量白介素-1β,术后8、48 h,1周处死动物分别行HE染色及Western blot检测.结果 白介素-1β包裹血管外膜后出现血管平滑肌细胞的增殖、迁移,通道蛋白JAK2、STAT3在不同时间点出现不同程度的磷酸化,经Western blot检测并行灰度分析,p-JAK2相对灰度值对照组(0.337 ±0.216),8h组(1.764±0.513),1周组(0.451±0.229)；p-STAT3相对灰度值对照组(0.125±0.870),24h组(1.909±0.309),2周组(0.448±0.516),各组间有明显差异(P＜0.05).加用抑制剂后,8h组p-JAK2相对灰度值实验侧(0.085±0.031),对照侧(1.416±0.468),48 h组p-STAT3相对灰度值实验侧(0.460±0.065),对照侧(2.425±0.638),提示JAK2、STAT3的磷酸化水平被明显抑制(P＜0.05),平滑肌细胞变化程度下降.结论 炎性因子白细胞介素-1β经动脉外膜给药可致动脉平滑肌细胞增殖、迁移,这种改变与JAK2-STAT3信号通路有直接关系.

Objective To determine the effect of renal denervation on hypertension in the middle-aged rats.Methods A total of 25 spontaneous hypertension rats(SHR) and 25 Wistar kyoto rats(WKY) aging 30-week-old male rats,weighing 350 to 420 g were randomly divided into 5 groups randomly,that is,1-day group,4-day group,9-day group,16-day group,and 32-day group(n=10,including 5 SHR and 5 WKY rats in each group).The implementation of the renal denervation was on the second day with 10% phenol ethanol solution.Blood pressure was measured by a non-invasive tail blood pressure meter(BP-98A).The plasma and renal tissue norepinephrine(nonadrenaline,NE) content and rennin activity were detected by ELISA.The expression of α1-and β1-adrenoreceptor(α1-R and β1-R)in rat aortic smooth muscle were determined by RT-PCR and Western blotting respectively for their mRNA and protein levels.Results NE content and renin activity in the plasma and renal tissue were significantly higher in middle-aged SHR than in middle-aged WKY rats(P<0.05).However,the expression of the aorta α1-R and β1-R at the mRNA and protein levels had no significant difference in middle-aged SHR and WKY rats(P>0.05).Rapid decline in blood pressure was observed in middle-aged SHR after denervation(P<0.05),and NE content and renin activity in the plasma and renal tissue was significantly decreased(P<0.05),but the expression of the aorta α1-R was up-regulated(P<0.05),and β1-R had no difference(P>0.05).In the chronic denervation period,the blood pressure as well as renal NE content and renin activity were gradually higher than normal levels(P<0.05).The expression of α1-R and β1-R were up-regulated which ultimately higher than initial levels(P<0.05).The expression of α1-R and β1-R protein was similar with the expression of mRNA.Conclusion Renal denervation attenuates the high blood pressure temporarily in the middle-aged SHR.During the acute period,α1-R is up-regulated.However,blood pressure is gradually increased in chronic period with the up-regulation of α1-R and β1-R.Changes in the blood pressure are consistent with the changes in the NE and renin activity.

Objective To study the effect of adenine nucleotide translocase 1(ANT1) gene over-expression on apoptosis of vascular smooth muscle cells(VSMC) in a rat carotid balloon injury model induced by adenovirus plasmid.Methods Seventy-two SD rats were randomly divided into normal group,non-transfection group,Ad-GFP transfection group and Ad-ANT1 transfection group(18 in each group).ANT1 gene was transfected into rat carotid arteries with Ad-ANT1 adenovirus after a rat carotid balloon injury model was established.The arteries were harvested on days 7,14 and 28 after operation.Expression of ANT-1,BAX,and Bcl-2 in arteries was detected by RT-PCR,Western blotting,and immunohistochemistry,respectively,with HE staining.Apoptosis of VSMC in tunica intima and tunica media of the model was assayed with TUNEL staining.Results The ANT1 gene was significantly expressed in rat carotid arteries after Ad-ANT1 transfection and reached its peak level on day 14,which was significantly higher in Ad-ANT1 transfection group than in Ad-GFP transfection group and balloon injury group(P<0.01).The expression level of BAX was significantly higher in Ad-ANT1 transfection group than in Ad-GFP transfection group and balloon injury group on days 7 and 14 after transfection(P<0.05).The expression level of Bcl-2 was higher in Ad-ANT1 transfection group than in normal group(P<0.05).However,no significant difference was found in expression level of Bcl-2 between the two groups(P>0.05).The apoptosis rate of VSMC in tunica intima and tunica media of the model was significantly higher in Ad-ANT1 transfection group than in the other 3 groups(P<0.05).The tunica intima/ tunica media area ratio in the model was lower in Ad-ANT1 transfection group than in Ad-GFP transfection group and balloon injury group on days 14 and 28 after transfection(P<0.05).Conclusion Adenovirus plasmid-induced over-expression of ANT1 gene induces apoptosis of VSMC in tunica intima/ tunica media of the model by up-regulating the expression of BAX.

<正>目的:研究IL-1β经血管外膜给药致VSMC的改变及其与JAK2-STAT3通路的关系。方法:SD大鼠24只,分离左侧颈总动脉,实验组血管外膜包裹含IL-1β(2.5μg)的琼脂缓释悬液,对照组包裹空白琼脂悬液,术后2、8、24、48 h,1、2周分别处