不同脏器来源的小鼠老化淀粉样变性纤维特征的研究

Characteristics of mouse senile amyloid fibrils from the defferent organs

目的 利用小鼠老化淀粉样变性发病模型,研究不同脏器来源的高密度载脂蛋白2淀粉样变性疾病(AApoAⅡ)淀粉样变性纤维的特征.方法 经尾静脉注射AApoAⅡ淀粉样变性纤维7个月后,SAMR1.P1-Apoa2c转基因小鼠被诱导成为老化淀粉样变性动物模型.免疫组织化学染色、刚果红染色判定其淀粉样变性程度;Pras法提取各脏器(心、肝、脾、肺、肾、胃、肠、舌、皮肤、粪)AApoAⅡ淀粉样变性纤维、经ThT法计算纤维含量后,利用Western blot法观察其分子量特征并利用二次传播实验检测其传播性.结果 成功制作了重度小鼠老化淀粉样变性动物模型.与其他脏器来源的AApoAⅡ淀粉样变性纤维相比,来源于粪的AApoAⅡ淀粉样变性纤维具有更小分子量的单体,并具备更强的传播力(P<0.05).结论 具有更小分子质量单体的粪来源小鼠AApoAⅡ淀粉样变性纤维具备更强的传播力.这为淀粉样变性疾病机制的研究开辟了新的研究方向.

Objective To study characteristics of mouse ApoAⅡ amiloidosis (AApoAⅡ) amyloid fibrils from the defferent organs by using mouse senile amyloidosis model. Methods SAMR1. P1-Apoa2c transgenic mice were injected intravenously with AApoAⅡamyloid fibrils to induce AApoAⅡ amyloidosis. Seven months later, the mice were sacrificed and the deposition of amyloid fibrils was identified by histology and immunohistochemistry and by Congo Red staining. After AApoAⅡ amyloid fibril fractions were isolated by Pras method, the quantity of amyloid fibrils was calculated by ThT, the molecular weight of amyloid fibrils was detected by western blot electrophoresis, the transmissibility was determined by secondary transmission examination. Results Severe mouse senile amyloidosis model was established. Compared to amyloid fibrils from heart, liver, spleen, lung, kindey, stomach, intestine, tongue and skin, AApoA Ⅱ amyloid fibrils from feces has smaller amyloid fibrils and higher transmissibility. Conclusions AApoAⅡ amyloid fibril fractions from feces has smaller molecular monomers and higher transmissibility. This may help to farther study in the mechanism of amyloidosis.