长春西汀对糖尿病大鼠静脉桥移植术后再狭窄的影响

Study on the effect of vinpocetine on the restenosis of venous bypass grafts in diabetic rats

目的探讨长春西汀(Vinp)对糖尿病静脉桥移植术后再狭窄的影响及可能作用机制。方法 36只SD大鼠随机分为对照组和Vinp组,通过建立糖尿病模型进行自体颈外静脉-颈总动脉移植,分别以生理盐水或者Vinp进行腹腔注射,于术后0周、2周及4周取移植静脉桥制作病理切片,测量内膜厚度,免疫组化法检测增殖细胞核抗原(PCNA)蛋白表达,通过细胞增殖指数定量描述。Western blot检测核转录因子(NF)-κB的磷酸化水平。结果 Vinp干预后明显减少糖尿病血管桥内膜增厚[术后2周:(17.06±5.10)μm vs.(39.79±7.84)μm,P<0.01;4周:(30.94±5.18)μm vs.(63.67±18.09)μm,P<0.01],同时还降低糖尿病静脉桥PCNA蛋白的表达[术后2周:(21.07±1.38)%vs.(28.13±1.35)%,P<0.01;4周:(31.73±1.38)%vs.(63.67±18.09)%,P<0.01],并抑制NF-κB的磷酸化(术后2周:1.08±0.42 vs.0.84±0.12,P<0.01)。结论 Vinp能有效抑制糖尿病静脉桥术后内膜增厚,其机制可能与抑制NF-κB通路,从而抑制炎症反应有关。

Objective To expose the effect and its potential mechanism of vinpocetine（Vinp） on the restenosis of dia-betic grafted veins. Methods Thirty-six Sprague-Dawley rats were randomized into saline control group and Vinp treat-ment group. The autologous jugular vein to carotid artery transplantation was performed in diabetic model rats. Normal sa-line or Vinp were intraperitoneally injected. The rats were sacrificed at 0, 2 or 4 weeks after surgery, then the grafted veinswere harvested. The pathological sections were used to detect the effect of Vinp on intimal hyperplasia. The protein expres-sion of proliferating cell nuclear antigen（PCNA） was detected by immunohistochemical method, and which was described bycell proliferation index. The phosphorylation of NF-κB was detected by Western blot assay. Results The treatment of Vinpon intimal hyperplasia in vivo was significant at two weeks after surgery（17.06±5.10） μm versus control group（39.79±7.84μm, P 0.01）,（30.94±5.18） μm versus（63.67±18.09） μm at four weeks after surgery（P 0.01）. Vinp treatment effectivelyreduced the protein expression of PCNA [2 weeks：（21.07±1.38）% vs.（28.13±1.35）%,P 0.01;4 weeks：（31.73±1.38）% vs.（63.67±18.09）%, P 0.01]. The treatment of Vinp inhibited phosphorylation of NF-κB at two weeks（1.08±0.42 vs. 0.84±0.12, P 0.01）. Conclusion Vinpocetine can effectively attenuate intimal hyperplasia in diabetic grafted veins, whichmight be related to its effect on inhibiting phosphorylation of NF-κB as well as inflammation.