摘要
目的研究右美托咪定(Dex)对早期内毒素休克大鼠肝组织核因子κB(NF-κB)表达及炎症因子的影响,以期为治疗脓毒症寻找新的治疗靶点。方法将40只Wistar大鼠随机分为正常对照组(生理盐水组)、脂多糖(LPS)组、Dex低剂量治疗组(DL)、中剂量治疗组(DM)和高剂量治疗组(DH)。生理盐水组注射0.9%生理盐水,LPS组注射LPS复制内毒素休克大鼠模型,DL、DM和DH治疗组在注射脂多糖建模成功后立即静脉泵入Dex(6.5μg/kg),再分别以4.5、1.5和0.5μg/(kg·h)的速度持续泵入6h。各组大鼠均在6h后处死,取下肝组织,免疫组织化学和蛋白质印迹法分析NF-κB表达情况,酶联免疫吸附测定法(ELISA)检测肝组织相关细胞因子,并在显微镜下观察肝组织的显微结构改变。结果免疫组织化学检测结果显示,LPS组NF-κB蛋白表达光密度D值为0.1419±0.0145,高于正常对照组的0.0983±0.0158,差异有统计学意义,P=0.001;DH组NF-κB蛋白表达光密度D值为0.1195±0.0169,低于LPS组,差异有统计学意义,P=0.044。LPS组阳性细胞百分比值为32.5273±7.4469,高于正常对照组的27.1284±4.6394,差异有统计学意义,P=0.015;DH组阳性细胞百分比值为29.3080±4.7789,低于LPS组,差异有统计学意义,P=0.044。蛋白质印迹法检测结果显示,LPS组NF-κB条带较其余各组明显增强,各治疗组中条带亮度均较弱,以DH组最明显。大鼠肝组织病理学结果显示,各治疗组与LPS组相比,DH组肝小叶结构清楚,肝细胞排列整齐,个别肝细胞内有脂滴,未见明显变性坏死肝细胞。LPS组大鼠肝组织中肿瘤坏死因子-α(TNF-α)为(13.0161±1.6848)pg/mL,高于正常对照组的(4.1222±1.0950)pg/mL,差异有统计学意义,P=0.011;DH治疗组TNF-α为(7.6711±1.2539)pg/mL,低于LPS组,差异有统计学意义,P=0.001。LPS组大鼠肝组织中白介素-6(IL-6)为(6.4028±1.1904)pg/mL,高于正常对照组的(3.3250±1.2523)pg/mL,差异有统计学意义,P<0.001;DH治疗组IL-6为(3.5121±0.6
Objective To study the effect of dexmedetomidine(Dex)on the expression of nuclear factor-κB(NF-κB)and inflammatory factors in the liver tissue of rats with early endotoxic shock,in order to find new therapeutic targets for the treatment of sepsis.Methods The 40 Wistar rats were randomly divided into normal control group(saline group),lipopolysaccharide group(LPS),Dex low-dose treatment group(DL),medium dose treatment group(DM)and high-dose treatment group(DH).The LPS group was injected with lipopolysaccharide(LPS)and 0.9%normal saline.Dex(6.5μg/kg)was infused into DL,DM and DH treatment groups immediately after LPS injection,and then continuously pumped at the speed of 4.5,1.5 and 0.5μg/(kg·h)for 6 h.The rats in each group were killed after 6 hours.The expression of NF-κB was analyzed by immunohistochemistry and Western blot.The related cytokines in liver tissue were detected by enzyme-linked immunosorbent assay(ELISA),and the microstructure of liver tissue was observed under microscope.Results The results of immunohistochemistry showed that the optical density Dvalue of NF-κB protein expression in the LPS group was 0.1419±0.0145,which was higher than the normal control group of 0.0983±0.0158,the difference was statistically significant,P=0.001.The DH group optical density D value of NF-κB protein expression was 0.1195±0.0169,which was lower than that of the LPS group.The difference was statistically significant,P=0.044.The percentage of positive cells in the LPS group was 32.5273±7.4469,which was higher than the 27.1284±4.6394 of the normal control group,and the difference was statistically significant,P=0.015.The percentage of positive cells in the DH group was 29.3080±4.7789,which was lower than the LPS group,the difference was statistically significant,P=0.044.The results of western blotting showed that the NF-κB band in the LPS group was significantly stronger than the other groups.The brightness of the band in each treatment group was weaker,with the DH group the most obvious.The histopatholo
作者
王欢
王丽
谭睿陟
雷贤英
WANG Huan;WANG Li;TAN Rui-zhi;LEI Xian-ying(Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)
出处
《社区医学杂志》
CAS
2021年第15期912-916,共5页
Journal Of Community Medicine
