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目的了解维生素D对大鼠急性心肌梗死的保护作用机制。方法选取脂多糖(LPS)诱导A7R5细胞Toll样受体(TLR)4表达量最高的浓度和时间点,应用1×10-7mol/L的1,25(OH)2D3进行干预。建立大鼠心肌梗死模型,随机分为2组,I组:心肌梗死模型组(n=16)、II组:维生素D治疗组(n=16),另设III组:假手术组(n=15)。4w后处死大鼠,观察大鼠心肌梗死面积(MIS)及心肌血清酶学变化。real-time PCR和Western blot方法检测TLR4、髓样分化因子(MyD)88和核因子活化B细胞κ轻链增强子(NF-κB)的mRNA和蛋白表达。结果在LPS诱导基础上,维生素D处理0、12和24 h后,TLR4、MyD88和NF-κB的mRNA水平分别为(22.0±5.1)、(15.1±5.1)和(8.0±4.2);(28.8±5.7)、(20.1±4.4)和(14.0±3.7);(25.2±5.3)、(17.7±4.5)和(10.2±3.7);TLR4、MyD88和NF-κB的蛋白水平变化同mRNA水平一致;维生素D可使实验性心肌梗死大鼠的MIS从(37.89±3.24)降至(12.25±1.34)(P<0.01),并改善心肌血清酶学变化(P<0.01);维生素D能够下调实验性心肌梗死大鼠心肌组织TLR4、MyD88和NF-κB的mRNA表达,分别从(4.61±0.42)、(3.81±0.36)和(3.86±0.51)降至(2.73±0.25)、(2.17±0.41)和(1.63±0.39);TLR4、MyD88和NF-κB的蛋白水平变化同mRNA水平一致。结论维生素D通过下调TLR4表达及相关的Myd88和NF-κB途径对大鼠的心血管产生保护作用。
Objective To investigate the protective effect of vitamin D on acute myocardial infarction in rats. Methods Lipopolysaccharide (LPS) was used to induce Toll-like receptor (TLR) 4 expression in A7R5 cells at the highest concentration and time points. The cells were treated with 1 × 10-7 mol / L 1,25 (OH) 2D3. The model of myocardial infarction in rats was established and randomly divided into two groups: group I: myocardial infarction model group (n = 16), group II: vitamin D treatment group (n = 16) and group III: sham operation group 15). After 4 weeks, the rats were sacrificed to observe the changes of myocardial infarct size (MIS) and myocardial enzymology. Real-time PCR and Western blot were used to detect the mRNA and protein expression of TLR4, myeloid differentiation factor (MyD) 88 and nuclear factor-activated B cell kappa light chain enhancer (NF-κB). Results On the basis of LPS induction, the mRNA levels of TLR4, MyD88 and NF-κB were (22.0 ± 5.1), (15.1 ± 5.1) and (8.0 ± 4.2) days after treatment with vitamin D for 0, 12 and 24 h, respectively (20.1 ± 4.4) and (14.0 ± 3.7), (25.2 ± 5.3), (17.7 ± 4.5) and (10.2 ± 3.7), respectively. The changes of TLR4, MyD88 and NF- Vitamin D decreased the MIS of experimental myocardial infarction rats from (37.89 ± 3.24) to (12.25 ± 1.34) (P <0.01), and improved myocardial enzymological changes (P <0.01). Vitamin D reduced the experimental The mRNA expressions of TLR4, MyD88 and NF-κB in myocardium of myocardial infarction rats decreased from (4.61 ± 0.42), (3.81 ± 0.36) and (3.86 ± 0.51) to (2.73 ± 0.25), (1.63 ± 0.39). The changes of TLR4, MyD88 and NF-κB protein levels were consistent with the mRNA levels. Conclusion Vitamin D can protect rat cardiovascular system by down-regulating TLR4 expression and related Myd88 and NF-κB pathway.