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干细胞联合双药纳米组装体对大鼠急性心肌梗死后心室重构和心功能的影响研究

Effects of stem cells combined with dual drug nanoassemblies on ventricular remodeling and cardiac function after acute myocardial infarction in rats

摘要:

目的:探讨干细胞联合双药纳米组装体对大鼠急性心肌梗死后心室重构和心功能的影响。方法:构建血管紧张素1-7(SAAl-7)多肽与替米沙坦共组装的双药纳米组装体。雄性SD大鼠100只随机分为假手术组、模型组、纳米组、干细胞组和联合组,每组各20只。模型组、纳米组、干细胞组和联合组均通过前降支结扎法建立急性心肌梗死模型,假手术组采取相同手术步骤但结扎线不结扎,干细胞组和联合组在结扎后于梗死区边缘注射20 μl干细胞,其他组采取相同方法注射等剂量的磷酸盐缓冲液(PBS)。手术建模当天开始,纳米组和联合组均尾静脉注射0.5 ml双药纳米组装体,假手术组、模型组和干细胞组均尾静脉注射等体积0.9%氯化钠溶液,术后均连续观察14 d。检测比较5组心功能指标[左室射血分数(LVEF)、左室短轴缩短率(FS)、左室舒张末期内径(LVEDD)、左室收缩末内径(LVESD)]、心室重构指标[左心室质量(LVW)、左室质量指数(LVWI)、心肌细胞横径(TDM)]、血清指标[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、超氧化物歧化酶(SOD)、谷胱甘肽、丙二醛、肌酐、丙氨酸氨基转移酶(ALT)]、心肌梗死面积和心肌细胞凋亡率等情况。结果:与假手术组比较,模型组的LVEF、FS、体质量、SOD和谷胱甘肽水平均降低(均 P<0.05),LVEDD、LVESD、LVW、LVWI、TDM、IL-6、TNF-α、丙二醛、肌酐、ALT、心肌梗死面积和心肌细胞凋亡率均升高(均 P<0.05)。与模型组比较,纳米组、干细胞组和联合组的LVEF、FS、体质量、SOD和谷胱甘肽水平均升高(均 P<0.05),LVEDD、LVESD、LVW、LVWI、TDM、IL-6、TNF-α、丙二醛、肌酐、ALT、心肌梗死面积和心肌细胞凋亡率均降低(均 P<0.05)。与纳米组和干细胞组比较,联合组的LVEF、FS、体质量、SOD和谷胱甘肽水平均升高(均 P<0.05),LVEDD、LVESD、LVW、LVWI、TDM、IL-6、TNF-α、丙二醛、肌酐、ALT、心肌梗死面积和心肌细胞凋亡率均降低(均 P<0.05)。 结论:干细胞联合双药纳米组装体可有效治疗急性心肌梗死大鼠,改善其心功能并减轻其心室重构,可能与其减轻炎症反应和氧化应激从而抑制心肌细胞凋亡和缩小心肌梗死面积有关。

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abstracts:

Objective:To investigate the effects of stem cells combined with dual drug nanoassemblies on ventricular remodeling and cardiac function after acute myocardial infarction in rats.Methods:A dual drug nano assembly of angiotensin 1-7 (SAAl-7) peptide and temisal was constructed. Male SD-rats (100 cases) were randomly divided into the sham group, model group, nano group, stem cell group, and combination group. And each group had 20 cases. Acute myocardial infarction rat models were established with anterior descending artery ligation in the model group, nano group, stem cell group, and combination group. The rats in the sham group took the same surgical steps but did not ligate the ligation line. In addition, rats in the stem cell group and combination group were injected with 20 μl of stem cells at the edge of the infarct area after ligation during the surgery. Rats in the other groups were injected with equal doses of phosphate buffered solution (PBS) by the same method. Starting from the day of surgical modeling, rats in nano group and combined group were injected with 0.5 ml of two-drug nano assemblies in the tail vein, while rats in the sham group, model group, stem cell group received a tail vein injection of an equal volume of 0.9% sodium chloride solution. After surgery, rats in all groups were continuously observed for 14 days. The cardiac function indicators, ventricular remodeling indicators, serum indicators, the myocardial infarction area, and the myocardial cell apoptosis rate of rats in all groups were detected and compared. The cardiac function indicators include left ventricular ejection fraction (LVEF), fraction shorting (FS), left ventricular end diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD). The ventricular remodeling indicators include left ventricle weight (LVW), left ventricular mass index (LVWI), and transdiameter of cardiomyocytes (TDM). The serum indicators include interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione, malondialdehyde, creatinine, and alanine aminotransferase (ALT).Results:Compared with the sham group, LVEF, FS, body mass, SOD, and glutathione levels in the model group were decreased (all P < 0.05), while LVEDD, LVESD, LVW, LVWI, TDM, IL-6, TNF-α, malondialdehyde, creatinine, ALT, myocardial infarction area, and myocardial cell apoptosis rate were increased (all P < 0.05). Compared with the model group, LVEF, FS, body mass, SOD, and glutathione levels in the nano group, stem cell group, and combination group were increased (all P < 0.05), while LVEDD, LVESD, LVW, LVWI, TDM, IL-6, TNF-α, malondialdehyde, creatinine, ALT, myocardial infarction area, and myocardial cell apoptosis rate were decreased (all P < 0.05). Compared with the nano group and stem cell group, LVEF, FS, body mass, SOD, and glutathione levels in the combination group were increased (all P < 0.05), while LVEDD, LVESD, LVW, LVWI, TDM, IL-6, TNF-α, malondialdehyde, creatinine, ALT, myocardial infarction area, and myocardial cell apoptosis rate were decreased (all P < 0.05). Conclusions:The combination of stem cells and dual drug nano assemblies can effectively treat acute myocardial infarction rats, improve their cardiac function, and reduce ventricular remodeling, which may be related to the reducing inflammatory response and oxidative stress inhibiting myocardial cell apoptosis and narrowing the area of myocardial infarction.

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