CAJ | 학술논문

背景：目前大量研究已经证实了中药制剂、骨髓间充质干细胞在防治血管再狭窄中的有效性，但二者联合应用防治糖尿病下肢动脉介入成形后血管再狭窄的相关研究较少。 　　目的：观察骨髓间充质干细胞联合益气养阴化瘀中药对犬糖尿病股动脉介入成形后血管再狭窄的影响。 　　方法：采用四氧嘧啶静脉注射结合球囊损伤建立糖尿病下肢血管再狭窄犬模型，造模成功后将22只犬随机分为3组，即糖尿病模型组(模型组，n=6)、益气养阴化瘀方治疗组(中药组，n=8)及益气养阴化瘀方联合骨髓间充质干细胞治疗组(联合治疗组，n=8)。分别在经皮腔内血管成形前、治疗后1，2，4，8周采用ELISA法检测血清中血管内皮生长因子水平。治疗后8周取股动脉血管标本进行病理血管形态学观察及增生程度的定量分析，并取心肝肾胰腺组织标本行病理切片苏木精-伊红染色评价干细胞静脉移植安全性。 　　结果与结论：治疗后1周，中药组和联合治疗组血清血管内皮细胞生长因子均开始升高，模型组治疗后4周开始升高(与治疗前比较，P<0.05)。同期各阶段，血清血管内皮细胞生长因子水平联合治疗组最高，模型组最低(P<0.05)。血管增生程度定量分析结果显示，治疗后8周新生内膜面积、新生内膜/中膜面积及狭窄率，模型组最高，联合治疗组最低(P<0.05)。干细胞移植安全性评价结果显示，治疗后8周心肝肾胰腺组织内部结构形态正常，未见组织坏死现象。综上，骨髓间充质干细胞联合益气养阴化瘀方比单纯中药治疗在防治糖尿病下肢动脉介入成形后再狭窄中作用更显著，是一种安全、有效的防治糖尿病下肢动脉介入成形后血管再狭窄发生的手段。
배경：목전대량연구이경증실료중약제제、골수간충질간세포재방치혈관재협착중적유효성，단이자연합응용방치당뇨병하지동맥개입성형후혈관재협착적상관연구교소。 　　목적：관찰골수간충질간세포연합익기양음화어중약대견당뇨병고동맥개입성형후혈관재협착적영향。 　　방법：채용사양밀정정맥주사결합구낭손상건립당뇨병하지혈관재협착견모형，조모성공후장22지견수궤분위3조，즉당뇨병모형조(모형조，n=6)、익기양음화어방치료조(중약조，n=8)급익기양음화어방연합골수간충질간세포치료조(연합치료조，n=8)。분별재경피강내혈관성형전、치료후1，2，4，8주채용ELISA법검측혈청중혈관내피생장인자수평。치료후8주취고동맥혈관표본진행병리혈관형태학관찰급증생정도적정량분석，병취심간신이선조직표본행병리절편소목정-이홍염색평개간세포정맥이식안전성。 　　결과여결론：치료후1주，중약조화연합치료조혈청혈관내피세포생장인자균개시승고，모형조치료후4주개시승고(여치료전비교，P<0.05)。동기각계단，혈청혈관내피세포생장인자수평연합치료조최고，모형조최저(P<0.05)。혈관증생정도정량분석결과현시，치료후8주신생내막면적、신생내막/중막면적급협착솔，모형조최고，연합치료조최저(P<0.05)。간세포이식안전성평개결과현시，치료후8주심간신이선조직내부결구형태정상，미견조직배사현상。종상，골수간충질간세포연합익기양음화어방비단순중약치료재방치당뇨병하지동맥개입성형후재협착중작용경현저，시일충안전、유효적방치당뇨병하지동맥개입성형후혈관재협착발생적수단。
BACKGROUND:At present, a great quantity of research has shown the effectiveness of traditional Chinese medicine and bone marrow mesenchymal stem cel s for vascular restenosis. However, studies concerning their combined application to restenosis after percutaneous transluminal angioplasty with diabetes mel itus are presently lacking. OBJECTIVE:To observe the effects of combined application of bone marrow mesenchymal stem cel s and benefiting-Qi nourishing-Yin and dissolving-congestion prescription on restenosis after percutaneous transluminal angioplasty in dogs with diabetes mel itus. METHODS:A dog model of vascular restenosis with diabetes mel itus was established by bal oon injury of femoral artery and intravenous injection of al oxan. After successful model induction, 22 dog models were randomly divided into three groups:model group (n=6), treatment with Chinese medicine (n=8), and combined treatment with bone marrow mesenchymal stem cel s and Chinese medicine (n=8). Serum vascular endothelial growth factor levels were measured using enzyme-linked immunosorbent assay preoperatively and at 1, 2, 4 and 8 weeks postoperation. Samples of vessels were taken to conduct pathomorphological observation and quantitative analysis of proliferation degree. Tissues, including heart, liver, kidney and pancreatic gland, were col ected to evaluate the safety of stem cel transplantation using hematoxylin-eosin staining at 8 weeks postoperation. RESULTS AND CONCLUSION:Serum vascular endothelial growth factor levels began to increase at 1 week postoperation in the Chinese medicine group and combined treatment group, at 4 weeks postoperation in the model group compared with preoperation (P<0.05). At al time points, serum vascular endothelial growth factor levels were highest in the combined treatment group, but lowest in the model group (P<0.05). Quantitative analysis of vascular proliferation demonstrated that at 8 weeks postoperation, new intimal area, new intimal/medial areas and stenosis rate were highest in the model group, but lowest in the combined treatment group at 8 weeks postoperation (P<0.05). Safety assessment of stem cel transplantation showed morphological structures of the heart, liver, kidneys and pancreas were normal, no necrosis. In a word, the effects of the combined application of bone marrow mesenchymal stem cel s and benefiting-Qi nourishing-Yin and dissolving-congestion prescription were much pronounced in preventing restenosis after percutaneous transluminal angioplasty in dogs with diabetes mel itus rather than single therapy of Chinese medicine. It is a safe and effective treatment to prevent vascular restenosis after percutaneous transluminal angioplasty in dogs with diabetes mel itus.