高脂血症易感(WSHc)大鼠自发性后肢瘫痪的病症特点研究

Study of the disease characteristics of spontaneous hindlimb paralysis in hyperlipidemia-susceptible( WSHc) rats

目的观察高脂血症易感(WSHc)大鼠种群中自发性后肢瘫痪大鼠的发病过程、病理特点,并初步研究其发病机制,探讨其应用与科研价值。方法在本中心培育的WSHc大鼠种群中,取8只自发性后肢瘫痪大鼠与8只来自同一家族的同周龄无瘫痪症状的大鼠,分别饲喂普通饲料和高脂饲料,观察对高脂血症的易感性;利用磁共振成像和病理组织学观察后肢瘫痪大鼠不同部位的中枢神经病变,TUNEL免疫组化法观察细胞凋亡水平;利用RT-PCR检测不同部位的中枢神经系统Caspase-1和IL-1β基因的表达,并利用Western Blot法检测蛋白水平的表达。结果后肢瘫痪的WSHc大鼠雌雄均可发病,对高脂饲料的敏感性与非后肢瘫痪的WSHc大鼠无显著差异,磁共振成像未见大脑及小脑存在显著性病变,病理组织学可见后肢瘫痪WSHc大鼠脊髓中后段大量炎症细胞浸润和TUNEL阳性表达,与非后肢瘫痪的WSHc大鼠比较,脊髓中后段Caspase-1与IL-1β基因的表达显著升高(P <0.05,P <0.01),且蛋白表达亦显著升高(P<0.05)。结论高脂血症易感WSHc大鼠自发性后肢瘫痪为进行性病变,其发病部位位于脊髓中后段,病理特征为炎症细胞浸润和神经元细胞变性凋亡,其发病机制可能与Caspase-1过度激活有关。

Objective To elucidate the onset process and pathological characteristics of spontaneous hindlimb paralysis in a hyperlipidemia-susceptible( WSHc) rat population,and to preliminarily study the pathogenesis mechanism.Methods In a WSHc rat population,eight spontaneous hindlimb paralysis rats and eight age-matched rats without paralysis symptoms from the same family were fed with normal chow or high-fat chow to examine their susceptibility to hyperlipidemia. Magnetic resonance imaging and histopathology were used to examine central neuropathy in different parts of hindlimb paralysis rats. TUNEL immunohistochemistry was used to detect apoptosis. The mRNA expression of Caspase-1 and IL-1β in the central nervous system was determined by RT-PCR,and the corresponding protein expression was determined by Western Blot. Results Both male and female WSHc rats with hindlimb paralysis developed the paralysis. The sensitivity to high-fat diet was not significantly different between WSHc rats with and without hindlimb paralysis. No significant lesions were observed in the brain and cerebellum by magnetic resonance imaging. Histopathology showed a large amount of inflammatory cell infiltration and TUNEL-positive staining in the middle and posterior spinal cord of hindlimb paralysis WSHc rats. Compared with the non-hindlimb paralysis WSHc rats,the mRNA and protein expression of Caspase-1 and IL-1β in the middle and posterior spinal cord was significantly increased( P < 0. 05,P < 0. 01) in the hindlimb paralysis WSHc rats. Conclusions Spontaneous hindlimb paralysis of hyperlipidemia-susceptible WSHc rats is a progressive lesion,which occurs in the middle and posterior spinal cord and is pathologically featured by inflammatory cell infiltration,neuronal degeneration and apoptosis. This pathogenesis may be related to excessive activation of caspase-1.