[1]黄鹤,田昭涛,姚咏明,等.肿瘤坏死因子-α诱导的蛋白-8样分子2促进热损伤小鼠CD4阳性T细胞凋亡[J].南方医科大学学报,2016,(10):1334.
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肿瘤坏死因子-α诱导的蛋白-8样分子2促进热损伤小鼠CD4阳性T细胞凋亡()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2016年10期
页码:
1334
栏目:
出版日期:
2016-10-15

文章信息/Info

Title:
Tumor necrosis factor-α-induced protein 8 like-2 promotes apoptosis of CD4 + T lymphocytes in mice with severe burn injury
作者:
黄鹤田昭涛姚咏明黎檀实
关键词:
肿瘤坏死因子α蛋白-8样分子2热损伤脓毒症免疫凋亡
Keywords:
tumor necrosis factor-alpha protein 8 like-2 burn injury sepsis immunity apoptosis
摘要:
目的探讨肿瘤坏死因子-α诱导的蛋白-8样分子2(TIPE2)对重度烫伤小鼠模型脾脏CD4+T淋巴细胞的凋亡的影响。方 法140只成年雄性BALB/C小鼠分为6组,应用小RNA干扰技术制作siTIPE2/过表达慢病毒,复制小鼠重度烫伤模型。分离 BALB/c小鼠脾脏CD4+T细胞,检测各组CD4+T淋巴细胞凋亡,Smad2/Smad3、磷酸(P)-Smad2/P-Smad3以及B淋巴细胞瘤-2 (Bcl-2)家族蛋白Bcl-2/Bim的表达。检测各组小鼠CD4+T内线粒体膜电位改变情况及细胞色素C的变化和各组小鼠CD4+T内 含半胱氨酸的天冬氨酸蛋白水解酶(caspase-3)、(caspase-8)、(caspase-9)的活化情况。结果siTIPE2-burn组CD4+T淋巴细胞凋 亡率为12.33%,较sham组外其余组减少,P-smad2/P-Smad3蛋白表达(灰度值)显著降低(P<0.01)。siTIPE2-burn组Bcl-2的蛋 白表达较其余组升高(P<0.05),Bim的表达则降低(P<0.05)。siTIPE2-burn组线粒体膜电位细胞色素C水平均较sham组外其 余组降低(P<0.05),caspase-3 活性较TIPE2-burn 组降低(P<0.01),caspase-8、caspase-9 活性较其余组降低(P<0.05)。TIPE2- burn组凋亡率最高,TIPE2-burn组Smad2/Smad3蛋白表达较sham组明显升高(P<0.05),P-smad2/P-Smad3蛋白表达较其余组 显著升高(P<0.05);CD4+T内线粒体膜电位较其余组降低(P<0.01),细胞色素C水平升高,caspase-3、caspase-8、caspase-9活性 较其他组均升高(P<0.05)。结论TIPE2作为一种重要的负向调控分子,可通过促进转化生长因子β即TGF-β/Smads信号传导 通路、线粒体相关凋亡途径加速T淋巴细胞凋亡。
Abstract:
Objective To investigate the effect of tumor necrosis factor-α-induced protein 8 like-2 (TIPE2) on apoptosis of CD4+ T lymphocytes in a murine model of severe burn injury. Methods A total of 140 male mice were randomly allocated into 6 groups. Small RNA interference technique was used to construct a siTIPE2-overexpressing lentivirus, and severe burn injury models were established in the mice. CD4+ T cells were purified from spleen of the mice, and the expressions of TIPE2, Smad2/ Smad3, P-Smad2/P-Smad3 and Bcl-2/Bimprotein in CD4 + Tregs were detected. The changes in mitochondrial membrane potential and cytochrome C in CD4 + T cells were detected, and the activities of caspase-3, caspase-8, and caspase-9 were analyzed. Results Down-regulation of TIPE2 promoted the apoptosis of CD4+ T lymphocytes in siTIPE2-burn group, in which the protein expressions of P-smad2/P-Smad3 decreased, Bcl-2 expression increased and Bim expression decreased significantly as compared with the other groups (P<0.01 or 0.05). The mitochondrial membrane potential and cytochrome C expression in CD4 + T cells were down-regulated in siTIPE2-burn group (P<0.05) with a lowered caspase-3 activity compared with TIPE2-burn group (P<0.01) and decreased caspase-8 and caspase-9 compared with the other groups (P<0.05). The apoptosis rate was the highest in TIPE2-burn group, whose Smad2/Smad3 was higher than that in the sham group (P<0.05) and the expression of P-smad2/P-Smad3 significantly increased compared with the other groups (P<0.05). In TIPE2-burn group, the mitochondrial membrane potential in CD4+ T cells was decreased (P<0.01), the expression of cytochrome C increased markedly (P<0.01), and the activities of caspase-3, caspase-8, and caspase-9 were all obviously higher than those in the other groups (P< 0.05). Conclusions As an important immunoregulatory molecule, TIPE2 can promote the apoptosis of CD4+T lymphocyte in mice with sever burn injury.

相似文献/References:

[1]高慧亭,徐丽姝,李东风,等.GLP-1对非酒精性脂肪肝大鼠肝氧化应激及TNF-α、TGF-β1的影响[J].南方医科大学学报,2013,(11):1661.

更新日期/Last Update: 1900-01-01