盐酸戊乙奎醚对内毒素血症大鼠全身炎性反应的影响

目的 探讨盐酸戊乙奎醚对内毒素血症大鼠血清TNF-α、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS),肺组织NF-κB亚基p65亲和肽(NF-κB p65)含量的影响. 方法 健康SD大鼠60只,采用随机数字表法分为5组(每组12只):对照组(C组)、内毒素组(LPS组)、LPS+低剂量盐酸戊乙奎醚组(P1组)、LPS+中剂量盐酸戊乙奎醚组(P2组)、LPS+高剂量盐酸戊乙奎醚组(P3组).LPS组腹腔注射内毒素8 mg/kg制备内毒素血症模型,C组给予等量生理盐水,P1组～P3组给予相应剂量的盐酸戊乙奎醚5 min后注射LPS,给药6h后处死动物取标本.采用ELISA检测血清TNF-α含量,采用比色法测血清iNOS活力,Western blot检测肺组织NF-κB p65含量,并观察肺组织病理学改变. 结果 与C组比较,LPS组、P1组、P2组、P3组血清TNF-α含量显著升高(P＜0.05),iNOS活力水平明显升高(P＜0.05),肺组织NF-κB p65表达明显增高(P＜0.05);与LPS组比较,P2组、P3组血清TNF-α、iNOS活力水平和肺组织NF-κB p65含量均下降(P＜0.05),而P1组TNF-α、iNOS活力和NF-κB p65表达水平,差异无统计学意义(P＞0.05);P2组、P3组间各指标表达水平比较,差异无统计学意义(P＞0.05);P2组、P3组肺组织病理学损伤程度明显轻于LPS组(P＜0.05). 结论 盐酸戊乙奎醚可能通过下调TNF-α、NF-κB p65的表达,减少iNOS活化来抑制内毒素休克大鼠全身炎症反应.

Effects of penequinine hydrochloride on systemic inflammatory response in endotoxemia rats

Objective To investigate the effects of penequinine hydrochloride on TNF-α and inducible nitric oxide synthase (iNOS) expression in endotoxemia rats,and the effects on nuclear factor kappa B p65 (NF-κB p65) expression in the lung tissue of these rats.Methods Sixty healthy SD rats were randomly divided into 5 groups:control group (group C),LPS group and P1 groups-P3 groups.Endotoxemia was induced by intraperitoneal LPS 8 mg/kg in LPS group,penequinine hydrochloride was infused intraperitoneally 5 min before LPS administration in P1-P3 groups.The animals were sacrificed 6 h later.The level of TNF-α in blood samples was determined using ELISA,and the level of iNOS activity in blood samples was evaluated using colorimetry.The expression of NF-κB p65 in the fight lung tissue was detected using Western blotting.The morphological changes of lung were inspected by means of optical microscope.Results Compared with control group,TNF-α content were significantly increased,iNOS activity were significantly increased in rat serum samples,and NF-κB p65 protein expression in the lung tissue were significantly increased (P＜0.05).Compared with LPS group,the expression of TNF-α,iNOS activity,and NF-κB p65 protein expression were significantly reduced in group P2 and P3,but group 1 had no significant difference.There was no significant difference in the indices mentioned above among group P2 and group P3.The inflammatory responses was significantly ameliorated in group P2 and P3 compared to LPS group.Conclusions Penequinine hydrochloride can inhibit endotoxin-induced systemic inflammatory response by blocking TNF-α,NF-κB p65 uncontrolling release and reducing iNOS activity.