摘要
目的观察肝X受体(liver X receptor,LXR)激动剂GW3965预处理对大鼠肝移植缺血再灌注损伤(ischemiareperfution injury,IRI)的影响及其对肝功能的保护作用。方法将雄性SD大鼠随机分为2组,GW3965预处理组于供体大鼠尾静脉注射LXR激动剂GW3965,0.3 mg/kg;对照组于相同部位注射相同剂量的生理盐水。参照改进的Kamada两袖套法建立大鼠原位肝移植模型,分别于肝移植术后3、6、24 h,采用全自动生化分析仪检测血清谷丙转氨酶(alanine aminotransferase,ALT)含量,ELISA法检测血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量,Western blot法测定移植肝脏组织中白细胞介素-1受体相关激酶-4(interleukin-1 receptor-associated kinase-4,IRAK-4)、干扰素调节因子3(interferon-regulator 3,IRF3)蛋白的表达,凝胶迁移试验(electrophoretic mobility shift assay,EMSA)测定核因子-kappa B(nuclear factor-κB,NF-κB)的相对活性度,并观察肝脏组织的病理学变化。结果与对照组比较,GW3965预处理组血清中ALT、TNF-α含量在各时间点均明显降低(P<0.05),肝脏组织中IRAK-4、IRF3蛋白的表达以及NF-κB相对活性度也明显降低(P<0.05);GW3965预处理组各时间点肝组织的损伤均较对照组明显减轻。结论 LXR激动剂GW3965可抑制TLR4信号通路中的IRAK-4、IRF3蛋白的表达水平和NF-κB的活化,从而减轻肝移植IRI,在肝脏移植IRI中起到保护作用。
Objective To observe the effect of pretreatment with liver X receptor agonist GW3965 on ischemia- reperfution injury （IRI） of transplanted liver and its protective effect on liver function. Methods Forty-eight male Sprague Dawley rats were divided into test and control groups. The rats in test group were injected i.v. with GW3965 at a dosage of 0. 3 mg/ kg, while those in control group with physiological saline. Rat model of in situ liver transplantation was established by modified Kamada twocuff technique, then determined for alanine aminotransferase （ALT） content by full- automatic biochemical analyzer, for tumor necrosis factor-ct （TNF-α） content in sera by ELISA, for expressions of interleukin- 1 receptor-associated kinase-4 （IRAK-4） and interferon-regulator 3 （IRF3） by Western blot, for relative activity of nuclear factor-KB （NF-KB） by electrophoretic mobility shift assay （EMSA）, and observed for pathological change in liver. Results As compared with those in control group, the ALT and TNF-ct contents in sera, the expression levels of IRAK-4 and IRF3 proteins in liver as well as the relative activity of rats in test group at various time points decreased significantly （each P 〈 0. 05）, while the lesion in liver tissue was relieved significantly. Conclusion LXR agonist GW3965 inhibited the expressions of IRAK-4 and IRF3 proteins and activation of NF-KB in TLR4 signal pathway, thus relieved the IRI and protected the transplanted liver.
出处
《中国生物制品学杂志》
CAS
CSCD
2013年第10期1430-1433,共4页
Chinese Journal of Biologicals
基金
重庆市卫生局医学科研项目(2011-20148)
关键词
肝X受体
激动剂
肝移植
缺血再灌注损伤
保护作用
Liver X receptor （LXR）
Agonist
Liver transplantation
Ischemia-reperfusion injury （IRI）
Protective effect
