1,25-二羟维生素D_3对Th1优势应答大鼠免疫功能的影响  

Immunomodulative effects of 1,25-Dihydroxyvitamin D_3 on the predominant Th1 response rat

作　　者：祁晓平[1] 黎介寿[1] 李培[1] 李刚[1] 孙正[1] 吴晓宇[1] 

机构地区：[1]南京大学医学院南京军区南京总医院普外科,南京210002

出　　处：《解放军医学杂志》2006年第11期1053-1055,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点基础研究发展规划项目资助(2003CB515502)

摘　　要：目的研究1,25-二羟维生素D31,25-(OH)2D3对内毒素(LPS)诱导的Th1优势应答大鼠T细胞免疫功能的影响。方法以1,25-(OH)2D3喂饲Lewis大鼠,1μg/d,共14天,对照组给予同体积的赋形剂,第15天大鼠腹腔注射LPS10ng/kg。每组25只大鼠,各留10只观察死亡率,其余大鼠6h后处死,留取标本,观察1,25-(OH)2D3对大鼠免疫细胞的细胞因子分泌、表型分化和细胞增殖的影响。结果注射LPS后观察96h,对照组大鼠24h内死亡5只(5/10),其余5只大鼠96h内均存活,实验组大鼠无死亡(0/10)。与对照组比较,实验组大鼠外周血IL-12和IFN-γ水平显著降低(3986±328pg/mlvs4160±289pg/ml,4840pg/ml±802pg/mlvs5264pg/ml±524pg/ml,P<0·05),IL-4水平显著升高(5·57±1·75pg/mlvs3·72±1·6pg/ml,P<0·05)。脾脏HE及PCNA免疫组化染色显示实验组大鼠白髓中淋巴细胞显著减少,PCNA阳性细胞呈局灶性或散在分布。流式细胞仪检测显示,实验组大鼠外周血CD4+CD25+淋巴细胞百分率(%)显著高于对照组(1·09±0·29vs0·73±0·00,P<0·01)。结论1,25-(OH)2D3能减轻致死剂量的LPS对大鼠的损伤,对Th1优势应答大鼠免疫细胞的细胞因子分泌、淋巴细胞增殖和细胞亚群分化具有调控作用。Objective To study the immunomodulative effects of 1,25-Dihydroxyvitamin D3[1,25-（OH）2D3] on the predominant Th1 response rats. Methods Lewis rats had been fed with 1,25-（OH）2D3 （1000ng per rat） for 14 days. The rats in control group were administered vehicle with the same volume as the drug to serve as the experimental group, and then LPS （10ng/kg） was administered intraperitoneally in both groups on the 15th day. 15 rats of each group were sacrificed 6h later and immunological index was measured. Mortality of the remaining ten rats in both group have been observed. Results There was no death in experimental group, while five control rats died at 24h （5/10, 50%）, and all the other five control rats survived at 96h. IL-12 and IFN-γ were decreased significantly in the experiment group compared with control （3986±328pg/ml vs 4160±289pg/ml, P=0.028; 4840±802pg/ml vs 5264±524pg/ml, P=0.020）, while IL-4 was increased （5.57±1.75pg/ml vs 3.72±1.62pg/ml, P=0.036）. In white pulp of the spleen of experimental rat the number of lymphocytes decreased significantly as shown with HE-staining, and the PCNA positive cells were distributed focally or dispersively. In addition, by using flow cytometer, it was found that CD4^＋ CD25^＋ positive lympbocytes were increased significantly in the spleen of experimental rats （1.09%±0.29% vs 0.73%±0.00%, P〈0.001）. Conclusion 1,25-（OH）2D3 could protect rats from a challenge of a lethal dose of LPS. It also has a comprehensive modulation effect on the production of cytokines, proliferation of lympbocytes and differentiation of lympbocytes subpopulations in predominant Th1 response rats.

关 键 词：骨化三醇 免疫调控 细胞因子类 

分 类 号：R346.53[医药卫生—基础医学]