1,25(OH)_2D_3减轻小鼠局灶性脑缺血再灌注后炎性反应

1,25(OH)_2D_3 ameliorates inflammatory response after focal cerebral ischemia reperfusion in mice

目的探讨1,25(OH)_2D_3对小鼠局灶性脑缺血再灌注后炎性反应的作用及其机制。方法造模前,通过一个月低维生素D饮食喂养,小鼠随机分为假手术组、局部缺血再灌注组(模型组)和1,25(OH)_2D_3组(治疗组)。造模前3 d始,假手术组和模型组每天腹腔注射2.4%乙醇,治疗组腹腔注射1,25(OH)_2D_3,共持续6 d。再灌注72 h后,Zea Longa法对鼠进行神经功能评分,干湿重法测量缺血侧脑组织含水量,RT-PCR法检测缺血侧半球IL-1βmRNA和TNF-αmRNA表达,采用Western blot法检测缺血侧半球NF-κB p65和Claudin-5的表达。结果与模型组比较,缺血再灌注后72 h,治疗组小鼠神经功能评分较低,缺血侧半球脑含水量、IL-1βmRNA、TNF-αmRNA和NF-κB p65表达显著减少,Claudin-5表达显著增加,差异均有统计学意义(P<0.05)。结论 1,25(OH)_2D_3减轻小鼠局灶性脑缺血再灌注损伤后炎性反应,其机制通过抑制NF-κB的活化有关。

Objective To investigate the effect and mechanism of 1,25 （OH） 2 D3 on inflammatory response after focal cerebral ischemia reperfusion in mice. Methods After one month of low vitamin D diet, mice were randomly divided into sham-operated group, vehicle group and 1,25 （OH）2 D3 treatment group. 3 days before and after the induction of focal cerebral ischemia reperfusion ,through intraperitoneal injection ,sham-operated group and vehicle group mice were given 2.4% ethanol every day, and 1,25 （OH）2D3 treatment group mice were given 1,25 （OH）2D3.72 h after ischemia reperfusion, neurological function deficits were assessed by Zea Longa method, brain water content was examined by wet and dry weight method,the expression of IL-1β mRNA and TNF-α mRNA in ischemic hemisphere was assessed by RT-PCR method, and Western blot method was used to detect the expression of NF-κB 1965 and Claudin-5. Results 72 h after ischemia reperfusion, in 1,25 （OH） 2 D3 group, neurological function deficits score, brain water content, the expression of IL-1β mRNA, TNF- α mRNA and NF-κB p65 in ischemic hemisphere were significantly lower or smaller than those in the vehicle group （P 〈 0. 05 ）, and the expression of Claudin-5 was significantly higher （ P 〈 0. 05 ）. Conclusion 1,25 （OH） , D3 ameliorates inflammatory response of focal cerebral ischemia reperfusion in mice and the mechanism may through inhibits the activation of NF-κB.