| 李帆,祖丽娅提 ?阿热甫江,陈红.丙泊酚通过 JAK激酶 -信号转导及转录活化因子信号通路抑制类风湿关节炎大鼠炎症反应及滑膜细胞凋亡[J].安徽医药,2022,26(6):1079-1083. |
| 丙泊酚通过 JAK激酶 -信号转导及转录活化因子信号通路抑制类风湿关节炎大鼠炎症反应及滑膜细胞凋亡 |
| Propofol inhibits inflammatory response and synovial cell apoptosis in rheumatoid arthritis mice through the JAK kinase-signal transducer and activator of transcription pathway |
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| DOI：10.3969/j.issn.1009-6469.2022.06.004 |
| 中文关键词: 二异丙酚 关节炎，类风湿 JAK激酶 -信号转导及转录活化因子信号通路 炎症反应 细胞凋亡 大鼠， Wistar |
| 英文关键词: Propofol Arthritis, rheumatoid JAK-STAT signaling pathway Inflammatory response Apoptosis Rats, Wistar |
| 基金项目:新疆维吾尔自治区自然科学基金项目( 2018D01C403) |
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| 中文摘要: |
| 目的研究丙泊酚对类风湿关节炎( RA)大鼠炎症反应、滑膜细胞凋亡、踝关节组织病理学变化及 JAK激酶( JAK)-信号转导及转录活化因子( STAT)信号通路的影响。方法于 2018年 7月至 2019年 7月，选取 36只 Wistar雄性大鼠，采用随机数字表法分为六组，每组 6只，分别为对照组、模型组、甲氨蝶呤组、丙泊酚低、中、高剂量组。除对照组外，其余各组均使用牛 Ⅱ型胶原诱导建立 RA大鼠模型，造模完成后，丙泊酚低、中、高剂量组分别按照 10 mg/kg、20 mg/kg、40 mg/kg腹腔注射给予大鼠丙泊酚，甲氨蝶呤组按照 7.5 mg/kg腹腔注射给予大鼠甲氨蝶呤，对照组及模型组腹腔注射给予大鼠等量生理盐水，每日定时给药 1次，连续给药 28 d后，对大鼠进行关节炎评分，检测大鼠血清肿瘤坏死因子 -α(TNF-α)、白细胞介素 -6(IL-6)及白细胞介素-1β(IL-1β)水平及脾脏、胸腺脏器指数，流式细胞术检测滑膜细胞凋亡率，苏木精 -伊红染色对大鼠踝关节进行组织病理学检查，蛋白质印迹法检测各组大鼠滑膜细胞的 JAK2、STAT3水平。结果连续给予 RA大鼠不同剂量的丙泊酚或甲氨蝶呤 28 d后，与模型组比较，丙泊酚低、中、高剂量组及甲氨蝶呤组 RA大鼠关节炎评分［(6.76±1.43)、(4.37±0.87)、(2.68±0.26)、(2.51± |
| 英文摘要: |
| Objective To study the effects of propofol on inflammatory response, synovial cell apoptosis, histopathological changesof ankle joint and JAK kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in rheumatoid arthritis mice.Methods From July 2018 to July 2019, thirty-six male Wistar mice were randomly assigned into 6 groups with 6 mice in eachgroup by random number table: control group, model group, methotrexate group, low-, middle-and high-dose propofol groups. Exceptfor the control group, all the other groups were induced by bovine type Ⅱ collagen to establish rheumatoid arthritis mouse model. Afterthe establishment of the model, the low-, middle-and high-dose groups of propofol were given intraperitoneal injection of propofol (10mg/kg, 20 mg/kg and 40mg/kg respectively), the methotrexate group was given intraperitoneal injection of methotrexate (7.5 mg/kg), andthe control group and model group were intraperitoneally injected with the same amount of normal saline. The medicine was given once a day for the respective group. After 28 days of administration, the arthritis score was measured, the levels of TNF-α, IL-6 and IL-1β in serum, the organ index of spleen and thymus, the apoptosis rate of synovial cells were detected by flow cytometry, and the histopathological examination of ankle joint was made by hematoxylin-eosin staining, Western blotting was performed to detect the levels of JAK2 and STAT3 in synovial cells of the mice in each group.Results After 28 days of continuous administration of different doses of propofol or methotrexate in rheumatoid arthritis mice, compared with the model group, the arthritis score [(6.76±1.43), (4.37±0.87), (2.68±0.26), (2.51±0.64) vs. (12.68±0.67)], the levels of TNF-α [(26.67±1.81) ng/L, (19.44±1.34) ng/L, (14.79±1.36) ng/L, (14.39±1.54) ng/L vs. (32.87±1.95) ng/L], IL-6 [(52.86±1.37) ng/L, (45.71±2.01) ng/L, (38.55±2.71) ng/L, (35.66±1.82) ng/L vs. (67.71±1.34) ng/L] and IL1β [(43.29±1.47) ng/L, (38.64±1.44) ng/L, (18.72±1.26) ng/L, (18.04±2.41) ng/L vs. (58.89±1.73) ng/L], splenic index [(33.27±2.84) %, (28.44±1.66) %, (18.73±1.18) %, (25.51±2.39) % vs. (38.64±4.68) %] and thymus index [(12.32±1.03) %, (10.67±0.81) %, (9.42± 0.75) %, (10.11±0.97) % vs. (14.62±1.37) %] and the apoptosis rate [(31.71±1.91) %, (24.84±1.91) %, (16.33±2.32) %, (15.62±2.52) % vs. (41.85±3.97) %] of synovial cells in low-, middle-and high-dose propofol groups and methotrexate group were significantly lower (P< 0.05). The histopathological test results showed that the histopathological conditions of ankle joint of rheumatoid arthritis mice in propofol groups and methotrexate group were significantly improved. Western blotting results showed that compared with the model group,the levels of JAK2 [(0.76±0.04), (0.59±0.04), (0.42±0.04), (0.41±0.05) vs. (1.19±0.16)] and STAT3 [(0.73±0.07), (0.55±0.05), (0.35± 0.08), (0.37±0.06) vs. (0.99±0.05)] in tissues of mice in propofol groups and methotrexate group were significantly decreased (P<0.05), and the changes in all indexes were dose-dependent on propofol.Conclusion Propofol can inhibit the inflammatory reaction and synovial cell apoptosis in rheumatoid arthritis mice, whose mechanism may be related to the regulation of JAK-STAT signal pathway in rheumatoid arthritis mice. |
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