生物可降解雷帕霉素输尿管支架对输尿管损伤后瘢痕形成的抑制作用

Biodegradable rapamycin-eluting ureteral stent inhibits scar formation after ureteral injuriy

目的 观察生物可降解雷帕霉素缓释输尿管支架对输尿管损伤后瘢痕形成的抑制作用.方法 原代培养尿路平滑肌细胞,噻唑蓝（MTT）法筛选雷帕霉素抑制尿路平滑肌细胞增殖的最佳药物浓度.再将构建的生物可降解雷帕霉素缓释输尿管支架和双J管分别置入输尿管损伤动物模型,评估两种支架抑制输尿管损伤后瘢痕形成情况.结果 MTT法检测显示雷帕霉素呈现剂量依赖性抑制尿路平滑肌细胞增殖,半数致死量（IC50）为23.3 mg/L.所有支架均成功置入输尿管,18周时,Masson三色和α-平滑肌肌动蛋白（α-SMA）免疫组织化学染色显示生物可降解雷帕霉素缓释输尿管支架侧胶原增生不明显,输尿管壁细胞排列有序,而双J管侧胶原纤维大量增生、层次紊乱.结论 生物可降解雷帕霉素缓释输尿管支架能有效抑制尿路平滑肌细胞的过度增殖和胶原沉积,从而预防输尿管瘢痕性狭窄的发生.

Objective To evaluate the effect of biodegradable rapamycin-eluting ureteral stent in inhibiting scar formation after ureteral injuries.Methods Smooth muscle cells were primary cultured.The inhibitory effect of rapamycin on the proliferation of smooth muscle cells was investigated by methyl thiazol tetrazolium （MTT） detection.And then,the optimal drug concentration was selected to construct drug-eluting stent.Biodegradable rapamycin-eluting ureteral stent and double-J stent were surgically implanted into the traumatic ureteral injury animal model,to evaluate the inhibitory effect in situ by histological tests.Results Smooth muscle cells were successfully cultured in vitro,and the results of MTT confirmed rapamycin could effectively inhibit the proliferation of smooth muscle cells depending on concentration.The IC50 was 23.3 mg/L.All stents were successfully implanted.At 18 weeks,masson trichrome and α-smooth muscle actin （α-SMA） immunohistochemical staining showed that biodegradable rapamycin-eluting ureteral stent,compared with double-J stent,can effectively inhibit the excessive proliferation of smooth muscle cells and collagen deposition.Conclusion Biodegradable rapamycin-eluting ureteral stent can effectively inhibit the excessive proliferation of smooth muscle cells and collagen deposition,thereby preventing ureteral scar stenosis.