HMGB1与间充质干细胞移植对大鼠急性心肌梗死心脏血管生成的影响
Influence of HMGB1 and MSCs transplantation on rat cardiac angiogenesis with acute myocardial infarction.
作者信息
Jiang Youxu, Wang Xiaoman, Jiang Xiaodong, Niu Shaohui, Zhang Lihua
机构信息
Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Emergency, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
出版信息
Pak J Pharm Sci. 2016 Jul;29(4 Suppl):1391-6.
To observe whether HMGB1could enhance the paracrine effect of MSCs when the Mesenchymal stem cells (Mesenchymal stem cells, MSCs) are pre-proccessed by High Mobility Group Box-1 (High Mobility Group Box-1, HMGB1). And to observe whether it can further increase the quantity of local angiogenesis in myocardial infarcts on the rat model with acute myocardial infarction, HMGB1 was combined with MSCs transplantation. MSCs in rats were cultivated with adherence and centrifugation method. Receptors of TLR4and RAGE in HMGB1 were tested. The MSCs were interfered by HMGB1 with different concentration gradient respectively, then the expression of VEGF was tested with ELISA method. SD male rats were divided into four groups: the model group, the MSCs transplantation group, the HMGB1 injection group, the HMGB1 injection plus MSCs transplantation group (n = 24), preparing rat model with acute myocardial infarction. The serum VEGF concentration levels were detected on the 3rd day, 7th and 28th day with ELISA method. On the 28th day after post operation the density of angiogenesis in infarction area was detected by immunohistochemal. (1) MSCs owned the expression of TLR4 and RAGE. (2) the secretion of VEGF increased significantly after the intervention of HMGB1 with concentration of 12.5 ng/mL, 25 ng/mL, 50 ng/mL, 100 ng/mL and 200ng/ml on MSCs compared with the control group. While the concentration was 400ng/ml or 800ng/ml, the secretion of VEGF decreased compared with the control group (P < 0.05). (3) detection of the serum VEGF on the 3rd or7th day after post operation was arranged: The results showed that: HMGB1 injection plus MSCs transplantation group > MSCs transplantation group >HMGB1 injection group >model group (P < 0.05). (4) the quantity of CD31 stained angiogenesis in HMGB1 injection plus MSCs transplantation group increased obviously. Combining MSCs transplantation, contributed to new angiogenesis of rats with acute myocardial infarction in myocardial infarction area and its near area in rats with acute myocardial infarction.
观察高迁移率族蛋白B1（High Mobility Group Box-1，HMGB1）预处理间充质干细胞（Mesenchymal stem cells，MSCs）时，HMGB1是否能增强MSCs的旁分泌作用。并观察其联合MSCs移植能否进一步增加急性心肌梗死大鼠模型心肌梗死灶局部血管新生数量，采用贴壁离心法培养大鼠MSCs，检测HMGB1中Toll样受体4（TLR4）和晚期糖基化终末产物受体（RAGE）。分别用不同浓度梯度的HMGB1干预MSCs，采用酶联免疫吸附测定（ELISA）法检测血管内皮生长因子（VEGF）表达。将雄性SD大鼠分为4组：模型组、MSCs移植组、HMGB1注射组、HMGB1注射+MSCs移植组（n=24），制备急性心肌梗死大鼠模型。术后第3天、第7天、第28天采用ELISA法检测血清VEGF浓度水平。术后第28天采用免疫组织化学法检测梗死区血管新生密度。（1）MSCs表达TLR4和RAGE。（2）与对照组比较，12.5 ng/mL、25 ng/mL、50 ng/mL、100 ng/mL和200 ng/ml浓度的HMGB1干预MSCs后，VEGF分泌明显增加；而浓度为400 ng/ml或800 ng/ml时，VEGF分泌较对照组减少（P<0.05）。（3）术后第3天或第7天血清VEGF检测结果显示：HMGB1注射+MSCs移植组>MSCs移植组>HMGB1注射组>模型组（P<0.05）。（4）HMGB1注射+MSCs移植组CD31染色的血管新生数量明显增加。联合MSCs移植有助于急性心肌梗死大鼠梗死区及其周边区域新生血管形成。
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