TLR4基因修饰BMSCs移植对大鼠急性心肌梗死后心功能的影响

陈文明; 蹇明辉; 仇治梅; 石蓓

doi:10.16016/j.1000-5404.201902029

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TLR4基因修饰BMSCs移植对大鼠急性心肌梗死后心功能的影响

基础医学 | 更新时间：2026-01-09

- TLR4基因修饰BMSCs移植对大鼠急性心肌梗死后心功能的影响
- Effect of bone marrow mesenchymal stem cells modified with Toll-like receptor 4 on cardiac function in rats after acute myocardial infarction
- 第三军医大学学报 2019年41卷第15期页码：1438-1444
- 作者机构：
- 作者简介：
- 基金信息：
  
  贵州省高层次创新型人才培养(黔科合人才(2015)4025)
- DOI：10.16016/j.1000-5404.201902029
  中图分类号：
- 收稿：2019-02-03，
  
  纸质出版：2019-08-15
- 稿件说明：
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陈文明, 蹇明辉, 仇治梅, 等. TLR4基因修饰BMSCs移植对大鼠急性心肌梗死后心功能的影响[J]. 第三军医大学学报, 2019,41(15):1438-1444.

Wenming CHEN, Minghui JIAN, Zhimei QIU, et al. Effect of bone marrow mesenchymal stem cells modified with Toll-like receptor 4 on cardiac function in rats after acute myocardial infarction[J]. Journal of Third Military Medical University, 2019, 41(15): 1438-1444.
陈文明, 蹇明辉, 仇治梅, 等. TLR4基因修饰BMSCs移植对大鼠急性心肌梗死后心功能的影响[J]. 第三军医大学学报, 2019,41(15):1438-1444. DOI： 10.16016/j.1000-5404.201902029.

Wenming CHEN, Minghui JIAN, Zhimei QIU, et al. Effect of bone marrow mesenchymal stem cells modified with Toll-like receptor 4 on cardiac function in rats after acute myocardial infarction[J]. Journal of Third Military Medical University, 2019, 41(15): 1438-1444. DOI： 10.16016/j.1000-5404.201902029.

摘要

Abstract

Objective

To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) modified with Toll-like receptor 4 (TLR4) on cardiac function in rats after acute myocardial infarction.

Methods

BMSCs were isolated from rat bone marrow and then cultured

in vitro

. The recombinant lentivirus vector carrying the target gene (Lv-EGFP-TLR4) and empty virus vector (Lv-EGFP) were transfected into BMSCs respectively. The expression of TLR4 in the supernatant of BMSCs cells transfected with Lv-EGFP-TLR4 was detected by ELISA. Adult SD rats were randomly divided into 3 groups (

=18): control group

Lv-EGFP-BMSCs group and Lv-EGFP-TLR4-BMSCs group. Lv-EGFP-BMSCs and Lv-EGFP-TLR4-BMSCs were injected into the periphery of myocardial infarction in rats

respectively. The control group was injected with the same amount of PBS. On the 7th day of transplantation

the expression of EGFP positive cells was tracked by fluorescence microscopy

and the express

ion of TLR4 was detected by Western blotting. Cardiac function was measured by echocardiography on 28 d after transplantation. Myocardial collagen fibrosis was observed by HE and MASSON staining. Serum levels of procollagen type Ⅰ carboxyl terminal peptide (PICP) and procollagen type Ⅲ amino terminal peptide (PⅢNT) were measured by ELISA.

Results

After transfection of BMSCs with Lv-EGFP-TLR4

the expression of TLR4 was increased significantly in the supernatant of BMSCs

and reached 31.55 pg/mL in 48 h after transfection. On the 7th day of cell transplantation

the green fluorescence intensity of BMSCs labeled with EGFP in infarct area was significantly higher in Lv-EGFP-TLR4-BMSCs group than in Lv-EGFP-BMSCs group

and no EGFP expression was seen in control group

and the expression of TLR4 protein was also significantly higher than that in Lv-EGFP-BMSCs group (

0.01). On the 28th day of cell transplantation

the Lv-EGFP-TLR4-BMSCs group showed significantly higher left ventricular ejection fraction and short-axis shortening rate when compared with the Lv-EGFP-BMSCs group

but left ventricular end-systolic diameter (LVDs

5.41±0.71) and left ventricular end-diastolic diameter (LVDd

7.11±0.79) were statistically decreased than the other group (6.66±0.91

8.06±0.9

0.01) The Lv-EGFP-TLR4-BMSCs group also had significantly lower serum levels of PICP (72.88

83.79 μg/L) and PⅢNT (7.33

9.51 μg/L) than those in Lv-EGFP-BMSCs group (

0.05). The severity of myocardial fibrosis in Lv-EGFP-TLR4-BMSCs group was also significantly lower than that in Lv-EGFP-BMSCs group.

Conclusion

Transplantation of TLR4 modified BMSCs can treat myocardial infarction

attenuate the severity of myocardial fibrosis

and thereby improve the cardiac function of myocardial infarction rats.

关键词

Keywords

references

唐一锋石蓓王冬梅 HMGB-1联合MSCs移植对急性心肌梗死大鼠心脏功能影响的实验研究重庆医学 2018 47 12 1583 1588 10.3969/j.issn.1671-8348.2018.12.005 唐一锋, 石蓓, 王冬梅, 等.HMGB-1联合MSCs移植对急性心肌梗死大鼠心脏功能影响的实验研究[J].重庆医学, 2018, 47(12):1583-1588.DIO:10.3969/j.issn.1671-8348.2018.12.005. TANG Y F, SHI B, WANG D M, et al .Experiment of effects of HMGB-1 combined with MSCs transplantation on cardiac function in rats with acute myocardial infarction[J ] .Chongqing Med, 2018, 47(12): 1583-1588.DIO: 10.3969/j.issn.1671-8348.20 18.12.005.

陈文明蹇明辉赵永超 Toll样受体4通过PI3K/Akt信号通路调节骨髓间充质干细胞凋亡遵义医学院学报 2017 6 617 621 10.14169/j.cnki.zunyixuebao.2017.0135 陈文明, 蹇明辉, 赵永超, 等.Toll样受体4通过PI3K/Akt信号通路调节骨髓间充质干细胞凋亡[J].遵义医学院学报, 2017(6):617-621.DOI:10.14169/j.cnki.zunyixuebao.2017.0135.

CHEN W M JIAN M H ZHAO Y C Toll-like receptor 4 regulats apoptosis of bone marrow mesenchymal stem cells through PI3K/Akt signaling pathways J Zunyi Med Univ 2017 40 6 617 621 10.14169/j.cnki.zunyixuebao.2017.0135 CHEN W M, JIAN M H, ZHAO Y C, et al .Toll-like receptor 4 regulats apoptosis of bone marrow mesenchymal stem cells through PI3K/Akt signaling pathways[J ] .J Zunyi Med Univ, 2017, 40(6):617-621.DOI:10.14169/j.cnki.zunyixuebao.2017.0135.

陈文明龙仙萍赵然尊 Toll样受体4激活Wnt/β-catenin信号通路促进骨髓间充质干细胞增殖中国老年学杂志 2018 03 666 668 10.3969/j.issn.1005-9202.2018.03.063 陈文明, 龙仙萍, 赵然尊, 等.Toll样受体4激活Wnt/β-catenin信号通路促进骨髓间充质干细胞增殖[J].中国老年学杂志, 2018(03):666-668.DIO:10.3969/j.issn.1005-9202.2018.03.063.

CHEN W M LONG X P ZHAO R Z Wnt/beta-catenin signaling pathway activated by Toll like receptor 4 promotes the proliferation of bone marrow mesenchymal stem cells Chin J Gerontol 2018 38 03 666 668 10.3969/j.issn.1005-9202.2018.03.063 CHEN W M, LONG X P, ZHAO R Z, et al .Wnt/beta-catenin signaling pathway activated by Toll like receptor 4 promotes the proliferation of bone marrow mesenchymal stem cells[J ] .Chin J Gerontol, 2018, 38(03):666-668.DIO:10.3969/j.issn.1005-9202.2018.03.063.

刘志江 , 石蓓 , 束波 , 等 . 高迁移率族蛋白1及其受体对大鼠骨髓间充质干细胞增殖及细胞因子水平的影响 [J ] . 中国动脉硬化杂志 , 2017 (4) , 25 ( 4 ): 337 - 342 .DOI: 10.3969/j.issn.1007-3949.2017.04.003 . 刘志江, 石蓓, 束波, 等.高迁移率族蛋白1及其受体对大鼠骨髓间充质干细胞增殖及细胞因子水平的影响[J].中国动脉硬化杂志, 2017(4), 25(4): 337-342.DOI: 10.3969/j.issn.1007-3949.2017.04.003.

LIU Z J , SHI B , SHU B , et al . Effects of high mobility group box 1 and its receptor on proliferation and cytokine levels of rat marrow mesenchymal stem cells [J ] . Chin J Arterioscler , 2017 , 25 ( 4 ): 337 - 342 .DOI: 10.3969/j.issn.1007-3949.2017.04.003 . LIU Z J, SHI B, SHU B, et al .Effects of high mobility group box 1 and its receptor on proliferation and cytokine levels of rat marrow mesenchymal stem cells[J ] .Chin J Arterioscler, 2017, 25(4):337-342.DOI: 10.3969/j.issn.1007-3949.2017.04.003.

龙仙萍邓文文赵然尊干扰Nrf2基因后骨髓间充质干细胞移植对大鼠心肌梗死后心肌凋亡的影响第三军医大学学报 2015 37 13 1319 1324 10.16016/j.1000-5404.201501143 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201501143 龙仙萍, 邓文文, 赵然尊, 等.干扰Nrf2基因后骨髓间充质干细胞移植对大鼠心肌梗死后心肌凋亡的影响[J].第三军医大学学报, 2015, 37(13):1319-1324.DOI:10.16016/j.1000-5404.201501143.

LONG X P DENG W W ZHAO R Effect of silencing Nrf2 gene on myocardial apoptosis after rat myocardial infarction with bone marrow mesenchymal stem cell transplantation J Third Mil Med Univ 2015 37 13 1319 1324 10.16016/j.1000-5404.201501143 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201501143 LONG X P, DENG W W, ZHAO R, et al .Effect of silencing Nrf2 gene on myocardial apoptosis after rat myocardial infarction with bone marrow mesenchymal stem cell transplantation[J ] .J Third Mil Med Univ, 2015, 37(13):1319-1324.DOI:10.16016/j.1000-5404.201501143.

邹松平王宇李春雨骨髓间充质干细胞旁分泌对急性心肌梗死心肌的保护作用中国组织工程研究 2014 18 23 3653 3659 10.3969/j.issn.2095-4344.2014.23.008 邹松平, 王宇, 李春雨, 等.骨髓间充质干细胞旁分泌对急性心肌梗死心肌的保护作用[J].中国组织工程研究, 2014, 18(23):3653-3659.DOI:10.3969/j.issn.2095-4344.2014.23.008.

ZOU S WANG Y LI C Y Bone marrow mesenchymal stem cells protect myocardial function in acute myocardial infarction through a paracrine mechanism Chin J Tissue Engineering Res 2014 18 23 3653 3659 10.3969/j.issn.2095-4344.2014.23.008 ZOU S, WANG Y, LI C Y, et al .Bone marrow mesenchymal stem cells protect myocardial function in acute myocardial infarction through a paracrine mechanism[J ] .Chin J Tissue Engineering Res, 2014, 18(23):3653-3659.DOI:10.3969/j.issn.2095-4344.2014.23.008.

MIAO C LEI M HU W A brief review:The therapeutic potential of bone marrow mesenchymal stem cells in myocardial infarction Stem Cell Res Ther 2017 8 1 1 6 https://link.springer.com/article/10.1186%2Fs13287-017-0697-9 MIAO C, LEI M, HU W, et al .A brief review:The therapeutic potential of bone marrow mesenchymal stem cells in myocardial infarction[J ] .Stem Cell Res Ther, 2017, 8(1):1-6.DIO:10.1186/s13287-017-0697-9.

XING A J XUE D WANG T Catalpol promotes the survival and VEGF secretion of bone marrow-derived stem cells and their role in myocardial repair after myocardial infarction in rats Cardiovascular Toxicology 2018 18 5 471 481 10.1007/s12012-018-9460-4 XING A J, XUE D, WANG T, et al .Catalpol promotes the survival and VEGF secretion of bone marrow-derived stem cells and their role in myocardial repair after myocardial infarction in rats[J ] .Cardiovascular Toxicology, 2018.18(5):471-481.DIO:10.1007/s12012-018-9460-4.

WOJTKOWIAK-GIERA A DERDA M AGNIESZKA KOLASA-WOłOSIUK Toll-like receptors in the brain of mice following infection with Acanthamoeba spp Parasitol Res 2016 115 11 4335 4344 10.1007/s00436-016-5217-9 WOJTKOWIAK-GIERA A, DERDA M, AGNIESZKA KOLASA-WOłOSIUK, et al .Toll-like receptors in the brain of mice following infection with Acanthamoeba spp[J ] .Parasitol Res, 2016, 115(11):4335-4344.DOI:10.1007/s00436-016-5217-9.

AKIRA S Toll-like receptors in innate immunity Adv Immunol 2001 78 1 1 56 10.1016/S0065-2776(01)78001-7 AKIRA S.Toll-like receptors in innate immunity[J].Adv Immunol, 2001, 78(1):1-56.DOI:10.1016/S0065-2776(01)78001-7.

MOLTENI M GEMMA S ROSSETTI C The role of toll-like receptor 4 in infectious and noninfectious inflammation Mediators Inflamm 2016 2016 1 9 10.1155/2016/6978936 MOLTENI M, GEMMA S, ROSSETTI C.The role of toll-like receptor 4 in infectious and noninfectious inflammation[J].Mediators Inflamm, 2016, 2016:1-9.DOI:10.1155/2016/6978936.

SHIRJANG S MANSOORI B SOLALI S Toll-like receptors as a key regulator of mesenchymal stem cell function:An up-to-date review Cellular Immunology 2017 315 1 10 10.1016/j.cellimm.2016.12.005 SHIRJANG S, MANSOORI B, SOLALI S, et al .Toll-like receptors as a key regulator of mesenchymal stem cell function:An up-to-date review[J ] .Cellular Immunology, 2017, 315:1-10.DOI:10.1016/j.cellimm.2016.12.005.

WANG Y C DING Y S LIU M L The molecular mechanism of different factors caused myocardial fibrosis Medical Recapitulate 2012 18 17 2736 2740 10.3969/j.issn.1006-2084.2012.17.003 WANG Y C, DING Y S, LIU M L.The molecular mechanism of different factors caused myocardial fibrosis[J].Medical Recapitulate, 2012, 18(17):2736-2740.DOI:10.3969/j.issn.1006-2084.2012.17.003.

J DÍEZ LAVIADES C MAYOR G Increased serum concentrations of procollagen peptides in essential hypertension:relation to cardiac alterations Circulation 1995 91 5 1450 1456 10.1161/01.CIR.91.5.1450 J DÍEZ, LAVIADES C, MAYOR G, et al .Increased serum concentrations of procollagen peptides in essential hypertension:relation to cardiac alterations[J ] .Circulation, 1995, 91(5):1450-1456.DOI:10.1161/01.CIR.91.5.1450.

赵丽晶安英陈雪叶黄素对异丙肾上腺素诱导的大鼠心肌纤维化的抑制作用中国临床药理学杂志 2018 34 5 544 547 10.13699/j.cnki.1001-6821.2018.05.016 赵丽晶, 安英, 陈雪, 等.叶黄素对异丙肾上腺素诱导的大鼠心肌纤维化的抑制作用[J].中国临床药理学杂志, 2018, 34(5):544-547.DOI:10.13699/j.cnki.1001-6821.2018.05.016.

ZHAO L J AN Y CHEN X Inhibitory effect of Lutein on myocardial fibrosis induced with isoprenaline in rats Chin J Clin Pharmacol 2018 34 5 544 547 10.13699/j.cnki.1001-6821.2018.05.016 ZHAO L J, AN Y, CHEN X, et al .Inhibitory effect of Lutein on myocardial fibrosis induced with isoprenaline in rats[J ] .Chin J Clin Pharmacol, 2018, 34(5):544-547.DOI:10.13699/j.cnki.1001-6821.2018.05.016.

郑兴张国元大鼠心肌梗死后血浆PⅢNP和PⅠCP的变化及其与心肌胶原含量的相关性研究临床心血管病杂志 2001 17 9 409 412 10.3969/j.issn.1001-1439.2001.09.010 郑兴, 张国元.大鼠心肌梗死后血浆PⅢNP和PⅠCP的变化及其与心肌胶原含量的相关性研究[J].临床心血管病杂志, 2001, 17(9):409-412.DOI:10.3969/j.issn.1001-1439.2001.09.010.

ZHENG X ZHANG G Y Changes of plasma concentrations of PⅢNP and PⅠCP after myocardial infarction and their relationship to the content of myocardial collagen in rat J Clin Cardiol 2001 17 9 409 412 10.3969/j.issn.1001-1439.2001.09.010 ZHENG X, ZHANG G Y.Changes of plasma concentrations of PⅢNP and PⅠCP after myocardial infarction and their relationship to the content of myocardial collagen in rat[J].J Clin Cardiol, 2001, 17(9):409-412.DOI:10.3969/j.issn.1001-1439.2001.09.010.

郑兴章同华秦永文心肌梗死患者血浆Ⅲ型前胶原氨基末端肽和Ⅰ型前胶原羧基末端肽含量的观察中华心血管病杂志 2001 29 4 213 215 10.3760/j:issn:0253-3758.2001.04.007 郑兴, 章同华, 秦永文, 等.心肌梗死患者血浆Ⅲ型前胶原氨基末端肽和Ⅰ型前胶原羧基末端肽含量的观察[J].中华心血管病杂志, 2001, 29(4):213-215.DOI:10.3760/j:issn:0253-3758.2001.04.007.

ZHENG X ZHANG T H QIN Y W Plasma concentrations of PⅢ NP and PⅠCP in patients with acute myocardial infarction Chin J Cardiol 2001 29 4 213 215 10.3760/j:issn:0253-3758.2001.04.007 ZHENG X, ZHANG T H, QIN Y W, et al .Plasma concentrations of PⅢ NP and PⅠCP in patients with acute myocardial infarction[J ] .Chin J Cardiol, 2001, 29(4):213-215.DOI:10.3760/j:issn:0253-3758.2001.04.007.

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