吡格列酮对脂多糖所致大鼠海马损伤的保护作用及其对iNOS和IL-1β表达水平的影响

Effects of Pioglitazone on LPS-induced Hippocampal Damages and iNOS and IL-1β Expression in Rats

目的研究过氧化体增殖物激活受体γ(PPARγ)激动剂吡格列酮(pioglitazone,pio)对大鼠脑室注射脂多糖(lipopolysaccharide,LPS)所致海马损伤的保护作用及对诱导型一氧化氮合酶(Inducible Nitric Oxide Synthase,iNOS)和白介素-1β(Interleukin-1β,IL-1β)表达水平的影响。方法雄性大鼠40只,随机分为4组,每组10只,即对照组,LPS模型组,LPS+Pio 40mg/kg组和LPS+pio 80mg/kg组。大鼠灌胃给予pio(40,80mg/kg)3周,脑室内注射LPS(5μl,30μg)1周后,取脑组织,制成石蜡切片,进行尼氏(Nissl)染色和胶质纤维酸蛋白(glial fibrillary acidic protein,GFAP)免疫组织化学染色,研究海马CA1区锥体神经元形态学改变和星形胶质细胞的活化、浸润情况。采用Western蛋白印迹检测方法观察IL-1β、iNOS的表达情况。结果大鼠脑室内注射LPS可引起海马CA1区星形胶质细胞的激活和浸润及椎体神经元的损伤,同时伴有IL-1β,iNOS的表达增加。Pio(40、80mg/kg连续应用1周)能减轻海马CA1区椎体神经元的损伤及星形胶质细胞的激活和浸润,抑制LPS引起的IL-1β、iNOS表达增加。侧脑室注射LPS后1周,LPS组大鼠海马CA1区IL-1β蛋白表达水平较对照组差异有统计学意义(P<0.01)。LSP+Pio 40mg/kg组和LSP+Pio 80mg/kg组大鼠海马CAI区IL-1β表达量较LPS模型组差别有统计学意义(P<0.01)。LSP+Pio 40mg/kg组和LSP+Pio 80mg/kg组大鼠海马CA1区iNOS表达量较LPS模型组差别有统计学意义(P<0.01)。结论Pio能够通过抑制LPS引起的IL-1β、iNOS的表达,减轻海马椎体神经元的损伤。

Objective To study the protective effect of pioglitazone （Pio） on lipopolysaccharide （LPS） -induced hippocampal damages and its influence to inducible nitric oxide synthase （iNOS） and interleukin - 1β （ IL - 1β） expression in rats. Methods Rats were by garage given Pio （40 mg/kg, 80 mg/kg） for 3 weeks, then were given intracerebroventricular injection of LPS （5μl, 30μg）. One week after the injection, Nissl staining and immunohistoehemieal technique for glial fibrillary acidic protein （GFAP） were employed to determine the morphology of pyramidal neurons and astrocyte activation and infiltration in hippocampal CA1. The expression of iNOS and IL - 1β was determined by Western blot method. Results Intracerebroven-tricular injection of LPS in rats elicited astrocyte activation and infiltration and loss of pyramidal neurons in hippocampal CA1, which was accompanied by the increase of iNOS and IL - 1β expression in hippocampal CA1. Pio （40 mg/kg, 80 mg/kg for consecutive one week） significantly reduced the LPS- induced astrocyte activation and infiltration, the loss of pyramidal neurons in hippocampal, and reversed the LPS - induced increases of iNOS and IL - 1β expression. After one week intracerebroventricular injection of LPS the IL - 1β expression in hippocampal CA1 in the LPS group was significantly different with that in the control group （ P 〈0.01）. The IL- 1β expressions in hippocampal CA1 in the Pio 40 mg/kg and 80 mg/kg groups were significantly different with that in the LIPS model group （ P 〈 0. 01 ）, and the iNOS expression in hippocampal CA1 were also significantly different with that in the LPS model group （ P 〈 0. 01 ）. Conclusion Pioglitazone can attenuate damages of pyramidal neurons in bippocampal CA1 by decrease the LPS -induced iNOS and IL- 1β expression.