拟阿尔茨海默病大鼠模型中肠源性内毒素血症水平的研究

Level of intestinal endotoxemia in Alzheimer disease rats

目的:探索在D-半乳糖和三氯化铝(AlCl3)联合使用制备拟阿尔茨海默病(AD)动物模型是否伴有肠源性内毒素血症(IETM)。方法:选用Wistar大鼠,腹腔注射D-半乳糖和AlCl3,连续90d,制备拟AD大鼠模型。给药结束后,通过Morris水迷宫观察模型大鼠学习记忆能力,鲎试剂法测定体内内毒素(LPS)水平,放射免疫法检测体内肿瘤坏死因子(TNF-α)、白细胞介素-1(IL-1)水平,半定量RT-PCR技术检测大鼠海马β淀粉样前体蛋白(APP)、早老素1(PS1)、β位点APP内切酶(BACE)的mRNA表达。结果:拟AD模型大鼠血浆中LPS水平升高,海马APP mRNA、PS1mRNA与BACE mRNA表达均明显升高(P<0.01)。结论:在D-半乳糖和AlCl3联合使用制备拟AD大鼠模型中有IETM的发生,并可能在AD发病中发挥重要作用。

AIM： The objective of the study was to explore whether intestinal endotoxemia participate in the development of Alzheimer disease. METHODS ： Adult Wistar rats were subjected to 90 days intraperitoneal injection with D - galactose and aluminum trichloride （ AlCl3 ） to establish the model of Alzheimer disease. After the administration, the study and memory ability in the rats were observed by Morris water maze. The level of lipopolysaccharide （LPS） in the sera of Alzheimer disease＇s rats was determined by tachypleus amebocyte lysate method. The level of tumor necrosis factor - α （TNF- α） and interleukin- 1 （IL- 1 ） in the sera were determined by radioimmunoassay. The expressions of amyloid β - protein precursor （ APP）, presenilin 1 （ PSi ） and β - site APP - cleaving enzyme （BACE） in hippecampus were detected by RT -PCR. RESULTS： Compared with the normal control, the level of LPS in the sera and the expressions of APP, PSI, BACE mRNA in the hippocampus were markedly increased （P 〈 0. 01 ）. CONCLUSION： The rat model of Alzheimer disease established by D - galactose and AlCl3 exposure is accompanied intestinal endotoxemia. This result suggests that intestinal endotoxemia plays an important role in the development of Alzheimer disease.