姜黄素对大鼠颈总动脉球囊损伤后血管内膜增生的影响

Effect of curcumin on the neointima formation after carotid balloon injuried in rats

目的观察姜黄素对大鼠颈总动脉球囊损伤后血管内膜增生及颈总动脉血管平滑肌细胞(VSMCs)磷酸化蛋白激酶-B(p-Akt)、B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的影响,探讨姜黄素影响VSMCs凋亡的可能机制。方法 48只SD大鼠随机分为假手术组、损伤组(对照组)、姜黄素低剂量组、姜黄素高剂量组。假手术组和对照组每天3ml生理盐水灌胃,姜黄素低剂量组和高剂量组每天分别给予3ml的100mg/kg和200mg/kg药物灌胃。分别在术后14d、28d取颈总动脉,通过HE染色和免疫组化结合图像分析技术观察血管形态学变化和测定p-Akt、Bcl-2、Bax的表达。结果术后14d和28d与对照组相比,相应时间点姜黄素高、低剂量组颈总动脉新生内膜增生面积(NA)及内膜与中膜面积比(NA/MA)均明显减小(P<0.05),p-Akt、Bcl-2表达减弱,Bax表达增强(P<0.05)。术后14d和28d与姜黄素低剂量组比较,相应时间点高剂量组p-Akt、Bcl-2表达减弱,Bax表达增强(P<0.05)。结论姜黄素可抑制球囊损伤后颈总动脉血管新生内膜增生,其作用机制可能是通过下调Bcl-2及上调Bax的表达,从而诱导血管损伤后增殖的VSMCs凋亡。

Objective To observe the effect of curcumin on neointimal hyperplasia and expression of p-Akt , Bcl-2 and Bax after carotid balloon injury , and to study the possible mechanisms of curcumin influencing the apoptosis of vascular smooth muscle cells （VSMCs）. Methods 48 healthy male SD rats were randomly divided into sham-operated group, injury group （control group）, low-dose curcumin group and high-dose curcumin group. Sham-operated group and control group re-ceived gastric perfusion with 3ml normal saline every day. Low-dose curcumin group and high-dose curcumin group received gastric perfusion of 100mg/kg and 200mg/kg curcumin （3ml） every day. 14 and 28 days after operation, the carotid tissues were acquired. Then the target vascular sections were stained with HE and observed the morphology changes. The expression of p-Akt, Bcl-2 and Bax in arterial wall cells were detected by immunohistochemistry. Results 14 and 28 days after balloon in-jury, both neointimal area and NA/MA significantly reduced in low-dose curcumin group and high-dose curcumin group com-pared with control group （P〈0.05）. Compared with control group, the expression of p-Akt, Bcl-2 positive cells decreased and Bax positive cells increased in the low-dose curcumin group and high-dose curcumin group after balloon injury （P〈0.05）. Com-pared with the low-dose curcumin group, the expression of p-Akt, Bcl-2 positive cells decreased and Bax positive cells in-creased in the high-dose curcumin group （P〈0.05）. Conclusion Curcumin can inhibit neointimal hyperplasia after carotid balloon injury. The possible mechanism is that inducing the apoptosis of VSMCs in vascular endomembrane after blood vessel in-jury through reducing Bcl-2 exprssion and increasing Bax expression.