紫杉醇對(duì)實(shí)驗(yàn)性自身免疫性腦脊髓炎大鼠的改善作用
本文選題:紫杉醇 + 實(shí)驗(yàn)性自身免疫性腦脊髓炎; 參考:《中國(guó)臨床藥理學(xué)雜志》2017年05期
【摘要】:目的研究紫杉醇對(duì)實(shí)驗(yàn)性自身免疫性腦脊髓炎(EAE)大鼠腦組織中共刺激分子白細(xì)胞分化抗原28(CD28)、細(xì)胞毒T淋巴細(xì)胞相關(guān)抗原4(CTLA-4)表達(dá)及血清中轉(zhuǎn)化生長(zhǎng)因子-β(TGF-β)含量的影響。方法按隨機(jī)數(shù)字法將Wistar大鼠分為5組:小中大3個(gè)劑量(紫杉醇1,2,4 mg·kg~(-1))實(shí)驗(yàn)組、正常組及模型組,每組10只。自造模后,實(shí)驗(yàn)組腹腔注射紫杉醇3個(gè)劑量,連續(xù)10 d。正常組及模型組均腹腔注射0.9%Na Cl 2 m L。取大鼠血清及腦組織,用流式細(xì)胞儀測(cè)定腦組CD28、CTLA-4含量;用放射免疫法測(cè)定血清TGF-β含量。結(jié)果小中大3個(gè)劑量實(shí)驗(yàn)組的神經(jīng)功能障礙評(píng)分分別為(2.30±1.16),(1.10±0.57),(0.90±0.57)分,均低于模型組的(3.90±0.99)分,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。小中大3個(gè)劑量實(shí)驗(yàn)組的腦組織學(xué)評(píng)分分別為(1.61±0.24),(1.44±0.22),(1.23±0.31)分,均低于模型組的(2.67±0.52)分,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。小中大3個(gè)劑量實(shí)驗(yàn)組的大鼠腦組織中CD28表達(dá)分別為33.9±4.49,26.4±4.14,20.7±4.21,均低于模型組得41.2±4.09,差異均具有統(tǒng)計(jì)學(xué)意義(P0.01)。小中大3個(gè)劑量實(shí)驗(yàn)組的大鼠腦組織中CTLA-4表達(dá)分別為4.3±1.42,5.8±1.81,6.4±1.68,均高于模型組的3.6±1.32,差異均具有統(tǒng)計(jì)學(xué)意義(P0.01)。小中大3個(gè)劑量實(shí)驗(yàn)組的血清中TGF-β含量分別為(11.20±1.80),(11.30±1.83),(14.10±1.87)ng·m L~(-1),均高于模型組的(11.00±1.73)ng·m L~(-1),差異均具有統(tǒng)計(jì)學(xué)意義(P0.01)。結(jié)論紫杉醇可降低EAE大鼠神經(jīng)功能障礙評(píng)分及腦組織學(xué)評(píng)分,紫杉醇對(duì)EAE大鼠的改善作用的機(jī)制可能為調(diào)節(jié)大鼠腦組織中CD28及CTLA-4的表達(dá)及血清TGF-β水平。
[Abstract]:Objective to study the effects of paclitaxel on the expression of co-stimulated leukocyte differentiation antigen 28 (CD28), cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and serum transforming growth factor- 尾 (TGF- 尾) in rats with experimental autoimmune encephalomyelitis (EAE). Methods Wistar rats were randomly divided into 5 groups: experimental group with 3 doses of paclitaxel 2mg kg ~ (-1), normal group and model group with 10 rats in each group. Three doses of paclitaxel were injected intraperitoneally in the experimental group for 10 days. In normal group and model group, 0.9% NaCl 2 mL was injected intraperitoneally. The contents of CD28CTLA-4 and TGF- 尾 were measured by flow cytometry and radioimmunoassay respectively. Results the scores of neurological dysfunction in the small, medium and large dose groups were (2.30 鹵1.16), (, 1.10 鹵0.57), (, 0.90 鹵0.57), lower than those in the model group (3.90 鹵0.99), the difference was statistically significant (P0.01). The scores of brain histology were (1.61 鹵0.24), (, 1.44 鹵0.22), (, 1.23 鹵0.31), lower than those of the model group (2.67 鹵0.52), respectively. The difference was statistically significant (P0.01). The expression of CD28 was 33.9 鹵4.49 ~ 26.4 鹵4.14 ~ (20.7 鹵4.21) in the brain of rats in three dose groups, which was lower than that in the model group (41.2 鹵4.09). The difference was statistically significant (P0.01). The expression of CTLA-4 in the brain of the rats in the small, medium and large dose groups was 4.3 鹵1.42U 5.8 鹵1.81 鹵1.68, respectively, which was significantly higher than that in the model group (3.6 鹵1.32). The difference was statistically significant (P0.01). The levels of TGF- 尾 in the small, medium and large dose groups were (11.20 鹵1.80), (, 11.30 鹵1.83), (, 14.10 鹵1.87) ng m L ~ (-1), higher than those in the model group (11.00 鹵1.73) ng m L ~ (-1), respectively (P0.01). Conclusion paclitaxel can decrease the scores of neurologic dysfunction and brain histology in EAE rats. The mechanism of paclitaxel on the improvement of EAE rats may be to regulate the expression of CD28 and CTLA-4 and the level of serum TGF- 尾 in EAE rats.
【作者單位】: 西南醫(yī)科大學(xué)附屬醫(yī)院神經(jīng)內(nèi)科;
【分類號(hào)】:R744.5
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