益气养阴化瘀方对糖尿病下肢动脉介入成形术后再狭窄的干预研究

Percutaneous transluminal angioplasty has become the treatment of diabetic lower extremity vascular stenosis or occlusion lesions. However, the long-term restenosis rate is still high, which become a big problem for clinicians. Post-angioplasty restenosis is primarily attributed to the direct damage of balloon or stent to the vessel wall, which cause differentiation, migration, and proliferation of perivascular smooth muscles. Ultimately, the neointimal hyperplasia and restenosis occurs. As soon as endothelial cells cover the damaged intima rapidly, intimal hyperplasia stops, which means rare or no intimal thickening phenomenon will happen, and restenosis will be reduced or prevented. There are a limitation of modern medicine in preventing and treating post-operation restenosis with anticoagulant drugs, a limited effect.So that has great clinical value to find safe and effective drugs to prevent restenosis.Benefiting-qi, nourishing-yin and dissolving-congestion prescription have obtained some good effect in the treatment of experimental rabbit lower limb atherosclerosis. In order to observe the restenosis after PTA, the first，Manufactured the dog model of lower limb atherosclerosis,and expand the study of the prescription , be to elucidate its mechanism and efficacy. And then studied on restenosis of lower extremity arterial disease after percutaneous transluminal angioplasty of diabetic patients, performed a prospective randomized controlled trial between the interventional group and the adding chines medicine treatment group, and follow-up the differences of long-term postoperative restenosis rate.Finally ,in order to find an effective method to improve the long-term patency rate.

下肢动脉介入成形术已成为治疗糖尿病下肢血管狭窄或闭塞病变的主要手段，但远期再狭窄率仍较高，成为临床治疗难点。成形术后再狭窄主要与球囊或支架对血管壁的直接损伤引起的血管平滑肌细胞过度增殖等有关。若血管内皮细胞能快速覆盖受损内膜，内膜增生反应即停止，就可减少或预防再狭窄形成。目前主要应用抗凝药物来预防术后再狭窄，效果有限。因此寻找新的有效的防止再狭窄的手段是非常必要的。在前期工作中我们观察了益气养阴活血化瘀方对兔糖尿病下肢动脉粥样硬化损伤后再狭窄模型的影响，取得了理想的结果。为进一步观察其对糖尿病下肢血管病变介入术后再狭窄的影响，本课题采用临床-动物试验相互验证的方法，以犬糖尿病下肢动脉病变介入后再狭窄模型及糖尿病下肢动脉病变的患者为研究对象，通过观察益气养阴活血中药治疗对介入成形术后远期再狭窄率的差异，验证其有效性，为临床应用提供依据。

下肢动脉介入成形术已成为治疗糖尿病下肢血管狭窄或闭塞病变的主要手段，但远期再狭窄率仍较高，成为临床治疗难点。目前主要应用抗凝药物来预防术后再狭窄，效果有限。因此寻找新的有效的防止再狭窄的手段是非常必要的。在前期工作中我们观察了益气养阴活血化瘀方对兔糖尿病下肢动脉粥样硬化损伤后再狭窄模型的影响，取得了理想的结果。为进一步观察其对糖尿病下肢血管病变介入术后再狭窄的影响，本课题采用动物试验的方法，以犬糖尿病下肢动脉病变介入后再狭窄模型为研究对象，研究益气养阴化瘀中药对介入成形术后远期再狭窄率的有效性及可能的机理，为进一步临床应用提供依据。本项目研究中将犬随机分为4组，即模型组，大、中、小剂量中药治疗组，采用高脂饮食及链脲佐菌素结合球囊损伤建立2型糖尿病下肢血管再狭窄模型。分别于术前、术后3天、1周、4周、8周采用酶联免疫吸附法（enzyme-linked immunosorbent assay , ELISA）检测血中血小板衍生生长因子（platelet-derived growth factor，PDGF）、内皮素（endothelin， ET）、一氧化氮（nitrogen monoxide ，NO）水平并进行统计分析。于术后5周、8周分别取血管标本进行病理血管形态学观察及增生程度定量分析。结果显示：血清PDGF、ET、NO水平术后3天显著升高（与术前比较，P<0.05）；PDGF、ET水平术后1周开始呈持续下降趋势，三个剂量治疗组血清PDGF、ET水平与术后3天比较，差异具有统计学意义（P<0.05），且同期模型组二者水平均显著高于三个治疗组；血清NO水平，模型组从术后1周开始呈持续下降趋势，三个中药组术后4周开始回升（与模型组、术后1w相比较，P<0.05）。病理形态学观察及定量分析可见术后5w、8w三个剂量中药治疗组血管内膜增生面积、内膜中膜面积比均低于模型组（P<0.05），且术后8w三个治疗组中膜面积也显著低于模型组。模型组术后8w血管内膜增生面积高于术后5w（P<0.05），三个治疗组血管内膜增生面积术后8w低于术后5w。结论：益气养阴化瘀方可通过降低术后急性期血清高水平PDGF、ET及升高远期NO水平起到抑制血管内膜增生 ，防治糖尿病下肢血管再狭窄的作用。