中华微生物学和免疫学杂志
中華微生物學和免疫學雜誌
중화미생물학화면역학잡지
CHINESE JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY
2008年
12期
1079-1083
,共5页
刘淑霞%郝军%郭惠芳%张玉军%刘青娟%唐丽娟%陈宁%吴海江%段惠军
劉淑霞%郝軍%郭惠芳%張玉軍%劉青娟%唐麗娟%陳寧%吳海江%段惠軍
류숙하%학군%곽혜방%장옥군%류청연%당려연%진저%오해강%단혜군
狼疮性肾炎%高迁移率族蛋白1%Toll样受体4%基质金属蛋白酶-2%基质金属蛋白酶组织抑制剂-2
狼瘡性腎炎%高遷移率族蛋白1%Toll樣受體4%基質金屬蛋白酶-2%基質金屬蛋白酶組織抑製劑-2
랑창성신염%고천이솔족단백1%Toll양수체4%기질금속단백매-2%기질금속단백매조직억제제-2
Lupus nephritis%High mobility group protein box 1%Toll-like receptor 4%Matrix met-alloproteinase-2%Tissue inhibitor of metalloproteinase-2
目的 探讨高迁移率族蛋白1(HMGB1)致红斑性狼疮肾损害的作用机制与Toll样受体4(Toll-like receptor 4,TLR4)表达的相关性.方法 ELISA检测12例健康对照组、16例系统性红斑狼疮(systemic lupus eqrthematosus,SLE)无肾脏损害和18例狼疮性肾炎(lupus nephritis,LN)患者血清中HMGB1、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶组织抑制剂-2(TIMP-2)的表达情况;流式细胞术检测外周血CD3/TLR4和CD14/TLR4表达情况;分离外周血单个核细胞(PBMC),RT-PCR检测HMGB1 mRNA的表达变化.结果 HMGB1 mRNA相对表达量及血清中HMGB1蛋白在LN组明显高于SLE组和健康对照组;流式细胞术显示CD14+的单核细胞表面HMGB1受体TLR4在LN组表达最高(P<0.05),且与尿蛋白呈正相关(P<0.01);LN患者血清中MMP-2和TIMP-2蛋白的浓度明显低于SLE和健康对照组,同时MMP-2/TIMP-2比值下降.HMGB1 mRNA及CD14+/TLR4+与MMP-2/TIMP-2比值均呈显著负相关;LN组患者血清中HMGB1蛋白水平与蛋白尿呈正相关,与MMP-2/TIMP-2比值呈显著负相关.结论 HMGB1是狼疮性肾炎发病中的重要细胞因子;HMGB1可能部分通过TLR4激活PBMC,降低MMP-2/TIMP-2的活性,从而引起蛋白尿.
目的 探討高遷移率族蛋白1(HMGB1)緻紅斑性狼瘡腎損害的作用機製與Toll樣受體4(Toll-like receptor 4,TLR4)錶達的相關性.方法 ELISA檢測12例健康對照組、16例繫統性紅斑狼瘡(systemic lupus eqrthematosus,SLE)無腎髒損害和18例狼瘡性腎炎(lupus nephritis,LN)患者血清中HMGB1、基質金屬蛋白酶-2(MMP-2)和基質金屬蛋白酶組織抑製劑-2(TIMP-2)的錶達情況;流式細胞術檢測外週血CD3/TLR4和CD14/TLR4錶達情況;分離外週血單箇覈細胞(PBMC),RT-PCR檢測HMGB1 mRNA的錶達變化.結果 HMGB1 mRNA相對錶達量及血清中HMGB1蛋白在LN組明顯高于SLE組和健康對照組;流式細胞術顯示CD14+的單覈細胞錶麵HMGB1受體TLR4在LN組錶達最高(P<0.05),且與尿蛋白呈正相關(P<0.01);LN患者血清中MMP-2和TIMP-2蛋白的濃度明顯低于SLE和健康對照組,同時MMP-2/TIMP-2比值下降.HMGB1 mRNA及CD14+/TLR4+與MMP-2/TIMP-2比值均呈顯著負相關;LN組患者血清中HMGB1蛋白水平與蛋白尿呈正相關,與MMP-2/TIMP-2比值呈顯著負相關.結論 HMGB1是狼瘡性腎炎髮病中的重要細胞因子;HMGB1可能部分通過TLR4激活PBMC,降低MMP-2/TIMP-2的活性,從而引起蛋白尿.
목적 탐토고천이솔족단백1(HMGB1)치홍반성랑창신손해적작용궤제여Toll양수체4(Toll-like receptor 4,TLR4)표체적상관성.방법 ELISA검측12례건강대조조、16례계통성홍반랑창(systemic lupus eqrthematosus,SLE)무신장손해화18례랑창성신염(lupus nephritis,LN)환자혈청중HMGB1、기질금속단백매-2(MMP-2)화기질금속단백매조직억제제-2(TIMP-2)적표체정황;류식세포술검측외주혈CD3/TLR4화CD14/TLR4표체정황;분리외주혈단개핵세포(PBMC),RT-PCR검측HMGB1 mRNA적표체변화.결과 HMGB1 mRNA상대표체량급혈청중HMGB1단백재LN조명현고우SLE조화건강대조조;류식세포술현시CD14+적단핵세포표면HMGB1수체TLR4재LN조표체최고(P<0.05),차여뇨단백정정상관(P<0.01);LN환자혈청중MMP-2화TIMP-2단백적농도명현저우SLE화건강대조조,동시MMP-2/TIMP-2비치하강.HMGB1 mRNA급CD14+/TLR4+여MMP-2/TIMP-2비치균정현저부상관;LN조환자혈청중HMGB1단백수평여단백뇨정정상관,여MMP-2/TIMP-2비치정현저부상관.결론 HMGB1시랑창성신염발병중적중요세포인자;HMGB1가능부분통과TLR4격활PBMC,강저MMP-2/TIMP-2적활성,종이인기단백뇨.
Objective To investigate the relationship between the effect of high mobility group protein box 1 (HMGBI) on the renal injure of systemic lupus erythematosus (SLE) and the expression of Toll-like receptor 4(TLR4). Methods The level of HMGB1, MMP-2 and TIMP-2 in serum from 16 pa-tients with SLE, 18 patients with lupus nephritis(LN) and 12 healthy people were measured by ELISA. The fresh peripheral blood mononuelear cell (PBMC) were isolated and the total RNA was extracted. Then the mRNA expression of HMGB1 was amplified by RT-PCR. Flow cytometry analysis was performed to study cell surface markers and the expression of TLR4. Results RT-PCR and ELISA results showed that the expres-sions of mRNA and level of HMGB1 protein in serum were higher in patients with LN than those in SLE and healthy people. The expression of TLR4 in CD14+ monecytes of patients with LN was higher than that with SLE and healthy people, while there were no significance in CD3+ T cells among LN, SLE and healthy peo-ple. The expressions of MMP-2 and TIMP-2 in serum of LN was lower than that in SLE and healthy people, at the same time the ratio of MMP-2/TIMP-2 decreased in LN group. HMGB1 mRNA and CD14+/TLR4+ was negatively correlated with the ratio of MMP-2/TIMP-2, and the level of HMGB1 in serum was positively correlated with proteinuria, while negatively correlated with the ratio of MMP-2/TIMP-2 in LN. Conclusion HMGB1 is one of the important cytokine in the pathogenesis of lupus nephritis. HMGBI might play a role in proteinuria of lupus nephritis in part via TLR4 pathway to activate monocytes and decrease the expression of MMP-2/TIMP-2.