摘要
目的研究脂多糖预处理骨髓间充质干细胞(MSC)后治疗急性心肌梗死(AMI)大鼠的机制。方法将大鼠MSC分为对照1组、脂多糖预处理为预处理1组、Toll样受体4封闭为封闭1组,定量分析多配体蛋白聚糖-4(syndecan-4)mRNA和蛋白表达。45只大鼠建立AMI后分别植入上述各组细胞,依次为对照2组、预处理2组和封闭2组,10周后测大鼠心功能指标;另30只AMI大鼠中,将MSC转染syndecan-4过表达质粒为过表达2组,沉默MSC syndecan-4基因为联合组,每组15只。MTT法测细胞增殖,光镜下观察大鼠新生血管密度,心肌梗死面积,计算死亡率。结果与对照1组和封闭1组比较,预处理1组MSC中syndecan-4基因和蛋白表达显著上升(P=0.000)。与对照2组和封闭2组比较,预处理2组大鼠各项心功能指标变化明显(P<0.01)。过表达2组MSC增殖率及大鼠新生血管密度较对照2组升高(P=0.009)。联合组较对照2组和预处理2组MSC增殖率、心肌梗死面积[(31.2±3.0)%vs(26.8±2.9)%和(19.7±2.5)%,P=0.013]和死亡率(20.0%vs 13.3%vs 20.0%,P=0.000)增高。结论脂多糖预处理能促进MSC中syndecan-4的表达,增强MSC移植在AMI中的治疗效果。
Objective To study whether lipopolysaccharide （LPS ） preconditioning improves the therapeutic effect of MSC transplantation in a rat model of acute myocardial infarction （AMI） . Methods MSC were divided into control group 1 ,LPS preconditioning group ,and Toll-like recep-tor 4 （TLR4） blocking group .Expression of syndecan-4 mRNA and protein in MSC was detected by quantitative analysis .The MSC were then divided into control group 2 ,LPS preconditioning group 2 ,and TLR4 blocking group 2 .Overexpressed plasmids in MSC-transfected syndecan 4 served as an overexpression group and silence syndecan 4 in MSC served as a combination group . Proliferation of MSC was assayed by MTT .The MSC were implanted into AMI rats .Angiogene-sis density was detected .Results The expression level of syndecan 4 mRNA and protein in MSC was significantly higher in LPS preconditioning group than in control group 1 and TLR4 blocking group 1 （P=0 .000） .The cardiac function was significantly better in LPS preconditioning group than in control group 2 and TLR4 blocking group 2 （P〈0 .01） .The proliferation rate of MSC and angiogenesis density were significantly higher in overexpression group than in control group 2 and TLR4 blocking group 2 （P=0 .009） .The proliferation rate of MSC was lower while the MI size was larger and the mortality was higher in combination group than in other groups （F=16 .739 , P=0 .013;20 .0% vs 13 .3% vs 20 .0% ,χ2 =13 .755 ,P=0 .000） .Conclusion LPS preconditioning up-regulates the syndecan 4 expression in MSC ,thus improving the therapeutic effect of MSC transplantation on AMI .
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2014年第10期1073-1077,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
国家自然科学基金(81100210)
