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目的:研究肝X受体(LXR)激动药22-(R)-羟化胆固醇对肝脏缺血再灌注(IR)模型大鼠的抗炎作用及其机制。方法:取大鼠用钳夹法建立肝脏IR模型,随机分为假手术组(3%羧甲基纤维素)、IR组(3%羧甲基纤维素)、阳性对照组(LXR激动药T0901317,50mg·kg-1)和22(-R)-羟化胆固醇高、中、低剂量(100、50、25mg·kg-1)预处理组,每组9只,各组大鼠建模前4h给予相应药物,建模后4h检测各组大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)以及肝组织髓过氧化物酶(MPO)水平,用实时定量基因扩增(PCR)仪检测大鼠肝组织中三磷酸腺苷(ATP)结合盒转运体A1(ABCA1)、ATP结合盒转运体G1(ABCG1)、细胞间黏附分子-1(ICAM-1)及诱导型一氧化氮合酶(iNOS)的mRNA水平,另设正常对照组进行比较。结果:与假手术组比较,IR组大鼠ALT、AST、MPO水平明显升高,ICAM-1和iNOS的mRNA表达明显增加(P均<0.01),ABCA1和ABCG1的mRNA表达无显著性变化;与IR组比较,22-(R)-羟化胆固醇高、中剂量预处理组和阳性对照组大鼠ALT、AST、MPO、ICAM-1和iNOS的mRNA表达均明显降低(P<0.05或P<0.01)。结论:22-(R)-羟化胆固醇可通过激活LXR发挥抗炎作用,进而降低肝脏IR损伤程度。
Objective: To investigate the anti-inflammatory effect and mechanism of 22- (R) -hydroxycholesterol, a kind of LXR agonist, on hepatic ischemia-reperfusion (IR) model rats. Methods: The rat model of hepatic IR was established by clamp method and randomly divided into sham operation group (3% carboxymethylcellulose), IR group (3% carboxymethylcellulose), positive control group (LXR agonist T0901317 , 50mg · kg-1 and 22 (-R) -hydroxycholesterol were pretreated with high, medium and low dose (100, 50, 25mg · kg-1) 4h were given the appropriate drugs, 4h after modeling, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver tissue myeloperoxidase (MPO) levels were detected in each group, with real-time Quantitative gene amplification (PCR) was used to detect the expression of ABCA1, ABCG1 and ICAM-1 in rat liver tissue Type nitric oxide synthase (iNOS) mRNA levels, another set of normal control group for comparison. Results: Compared with the sham operation group, the levels of ALT, AST and MPO in IR group were significantly increased, the mRNA expressions of ICAM-1 and iNOS were significantly increased (all P <0.01), but there was no significant change in ABCA1 and ABCG1 mRNA expression. Compared with IR group, the mRNA expressions of ALT, AST, MPO, ICAM-1 and iNOS in 22- (R) -hydroxylated cholesterol pretreatment group and positive control group were significantly decreased (P <0.05 or P <0.01). Conclusion: 22- (R) -hydroxylated cholesterol can exert anti-inflammatory effect by activating LXR, thereby reducing the degree of liver IR injury.