长春西汀对糖尿病大鼠静脉桥移植术后再狭窄的影响

摘要

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 veins were 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 by cell proliferation index. The phosphorylation of NF-κB was detected by Western blot assay. Results The treatment of Vinp on 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 effectively reduced 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, which might be related to its effect on inhibiting phosphorylation of NF-κB as well as inflammation.%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。