雷公藤红素缓解刀豆蛋白A诱导的小鼠急性肝损伤作用及其机制

将36只同一批次体重无明显差异的7周龄C57雄鼠随机分为6组,每组6只,即对照组,模型组,地塞米松(dexamethasone, DXM)组及雷公藤红素(celastrol, Cel)低、中、高剂量组(1.5、3、6 mg/kg),连续灌胃7 d后尾静脉注射20 mg/kg刀豆蛋白A(concanavalin A, ConA),地塞米松(0.5 mg/kg)于刀豆蛋白给药前1 h腹腔注射.注射8 h后处死小鼠,取其血清分别检测白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和丙氨酸氨基转移酶(ALT)及天冬氨酸转移酶(AST)的含量.取小鼠肝脾称重计算脏器系数,苏木精-伊红(HE)染色观察肝组织病理改变,用实时定量PCR法(RT-qPCR法)检测肝组织中相关基因mRNA的表达水平,流式细胞术检测脾脏中巨噬细胞的极化方向,从而研究雷公藤红素对刀豆蛋白A诱导的小鼠急性肝损伤的保护作用及其机制.结果显示:相较于正常组,模型组小鼠的肝组织明显发生急性肝炎,其小叶结构紊乱,肝细胞结构破坏,汇管区炎症细胞浸润,雷公藤...     

HRPT2, encoding parafibromin,is mutated in hyperparathyroidism-jaw tumor syndrome

We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.