青蒿素对大鼠自体移植静脉桥内膜增生的影响

Effects of artemisininon intimal hyperplasia in autogenous vein grafts in rats

目的探讨青蒿素对大鼠自体移植静脉桥内膜增生的影响。方法将雄性Sprague-Dawley(SD)大鼠32只建立自体静脉移植模型,随机分为两组:实验组(16只)和对照组(16只)。实验组于造模前1 d给予青蒿素100 mg/(kg·d)灌胃直至取材,对照组相同时间给予等体积生理盐水灌胃。两组动物分别于造模后2周和4周取材备检,每个时间点8只。应用图像分析仪计算新生内膜厚度,免疫组织化学方法检测平滑肌22α(SM22α)的表达变化及Western bolt检测SM22α蛋白表达变化情况。结果实验组术后2周、4周静脉桥新生内膜厚度与同期对照组比较明显减少[(20.79±1.88)μm vs.(35.23±2.66)μm,P<0.01;(37.06±2.22)μm vs.(46.23±2.54)μm,P<0.01]。SM22α在静脉桥平滑肌细胞有表达,实验组SM22α蛋白表达阳性率在术后2、4周较同期明显抑制下降[(59.20±5.76)vs.(26.12±3.72),P<0.01;(35.63±4.36)vs.(10.38±2.98),P<0.01]。实验组SM22α蛋白含量(SM22α/β-Actin)在术后2、4周较同期明显抑制下调[(0.58±0.1)vs.(0.39±0.06),P<0.01;(0.42±0.06)vs.(0.21±0.05),P<0.01]。结论青蒿素可明显抑制静脉桥内膜增生,原因可能与其抑制血管SM22α的表达下调,从而抑制平滑肌细胞增殖有关。

Objective To study the effects of artemisinin on intimal hyperplasia in autogenous vein grafts in rats. Methods Jugular vein-to-artery bypass grafting was performed on 32 male Sprague-Dawley rats.The rats were randomly divided into two groups:the treatment group(n = 16)and the control group(n = 16). The treatment group was given gastric perfusion artemisinin 100 mg/(kg · d)which began 1 day before operation and continued until harvesting,and the control group was given to the same volume with normal saline by the same way. At 2 or 4 weeks after surgery,vein grafts were harvested,with 8 rats for each time point. Computer image analysis system was applied tocalculate the thickness of neointima in the vein grafts,expression area of smooth muscle 22α(SM22α)was identified by immunohistochemical observationand the protein level of SM22α was detected by Western bolt. Results After 2 or 4 weeks,neointima thickness of the vein graft in the treatment group was significantly reduced compared with that of the control group[(20.79 ± 1.88)μm vs.(35.23 ± 2.66)μm,P<0.01;(37.06 ± 2.22)μm vs.(46.23 ±2.54)μm,P<0.01]. The expression of SM22α protein was detected in smooth muscle cells of vein graft after surgery.The positive rate of SM22α protein expression were significantly inhibited in the treatment group than that of the control group[(59.20 ± 5.76)vs.(26.12 ± 3.72),P<0.01;(35.63 ± 4.36)vs.(10.38 ± 2.98),P<0.01]. The protein expression levels of SM22α(SM22α/β-Actin)were significantly inhibitedin the treatment group than that of the control group[(0.58 ± 0.1)vs.(0.39 ± 0.06),P<0.01;(0.42 ± 0.06)vs.(0.21 ±0.05),P<0.01]. Conclusion Artemisinin could obviously inhibit hyperplasia of intimal thickness after venous transplantation,which may be related to inhibit the lower the expression of SM22α and inhibition of smooth muscle cell proliferation.