[1]胡 伟,张 涛,盛尚春,等.IGF-1R通过调控JAK/STAT信号通路对脓毒症大鼠作用机制的研究[J].现代检验医学杂志,2022,37(02):6-11.[doi:10.3969/j.issn.1671-7414.2022.02.002]
 HU Wei,ZHANG Tao,SHENG Shang-chun,et al.Mechanism of IGF-1R on Sepsis Rats by Regulating JAK / STAT Signaling Pathway[J].Journal of Modern Laboratory Medicine,2022,37(02):6-11.[doi:10.3969/j.issn.1671-7414.2022.02.002]
点击复制

IGF-1R通过调控JAK/STAT信号通路对脓毒症大鼠作用机制的研究()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年02期
页码:
6-11
栏目:
论 著
出版日期:
2022-03-15

文章信息/Info

Title:
Mechanism of IGF-1R on Sepsis Rats by Regulating JAK / STAT Signaling Pathway
文章编号:
1671-7414(2022)02-006-06
作者:
胡 伟张 涛盛尚春刘 翔丁贵梅代 琼
(宜宾市第二人民医院检验科,四川宜宾 644000)
Author(s):
HU Wei ZHANG TaoSHENG Shang-chun LIU Xiang DING Gui-mei DAI Qiong
(Department of Clinical Laboratory,the Second People’s Hospital of Yibin, Sichuan Yibin 644000,China)
关键词:
1型胰岛素样生长因子受体Janus激酶/信号转导和转录激活因子信号通路脓毒症
分类号:
R-332
DOI:
10.3969/j.issn.1671-7414.2022.02.002
文献标志码:
A
摘要:
目的 探究1 型胰岛素样生长因子受体(insulin-like growth factor 1 receptor,IGF-1R)通过调控Janus 激酶/ 信号转导和转录激活因子(janus kinase/signal transducer and activvator of transcription,JAK/STAT)信号通路对脓毒症大鼠作用机制。方法 将60 只实验大鼠随机分为假手术组(sham 组)、脓毒症大鼠模型组(sepsis 组)和脓毒症大鼠模型给予IGF-1R 干预组(IGF-1R 组),每组20 只。检测肺组织中IGF-1R 阳性细胞比例(免疫荧光染色法),检测血清中IL-6 和TNF-α 含量(ELISA 法),检测肺组织病理学改变(HE 染色法),TUNEL 检测各组细胞凋亡率,免疫印迹法检测组织中p-JAK1 和p-STAT3 蛋白表达。结果 组织中IGF-1R 阳性细胞在sham 组(58.32%±5.21%),sepsis 组(21.65%±8.73%)和IGF-1R 组(46.58%±6.72%)占比比较差异有统计学意义(F=141.7,P<0.000 1);和sham 组相比,sepsis 组大鼠肺组织中IGF-1R 阳性细胞在总细胞中所占比例减少(t=16.13,P<0.000 1),IGF-1R 组大鼠肺组织中IGF-1R 阳性细胞在总细胞中所占比例高于sepsis 组(t=10.12,P<0.000 1),差异均有统计学意义。血清中IL-6 在sham组(4.35±2.01pg/ml)、sepsis 组(9.81±4.26pg/ml)和IGF-1R 组(5.11±2.57pg/ml)中的含量比较差异有统计学意义(F=18.23,P<0.000 1),血清中TNF-α 含量在sham 组(2.31±1.12pg/ml)、sepsis 组(14.15±3.26pg/ml)和IGF-1R 组(6.58±2.15pg/ml)比较差异有统计学意义(F=130.7,P<0.000 1),和sham 组相比,sepsis 组IL-6 和TNF-α含量升高(t=5.18,21.98,均P<0.000 1);IGF-1R 组IL-6 和TNF-α 含量较sepsis 组降低,差异具有统计学意义(t=4.23,12.01, 均P< 0.000 1)。细胞凋亡率在sham 组(6.35%±2.51%)、sepsis 组(37.84%±6.62%)和IGF-1R 组(22.71%±4.28%)间比较差异有统计学意义(F=217.4,P<0.000 1)。和sham 组相比,sepsis 组细胞凋亡率增多(t=19.89,P<0.000 1);和sepsisi 组相比,IGF-1R 组大鼠肺组织中凋亡率降低(t=8.583,P<0.000 1)。肺组织中p-JAK1 在sham 组(0.15±0.11)、sepsis 组(0.33±0.16)和IGF-1R 组(0.17±0.13)中表达差异有统计学意义(F=10.70,P=0.000 1)。肺组织中p-STAT3在sham 组(0.12±0.10)、sepsis 组(0.28±0.15)和IGF-1R 组(0.19±0.12)中表达差异有统计学意义(F=8.230,P=0.000 7)。和sham 组相比,sepsis 组p-JAK1 和p-STAT3 蛋白表达增加(t=4.146,3.969,P=0.000 2, 0.000 3);IGF-1R 组大鼠肺组织中p-JAK1 和p-STAT3 蛋白表达低于sepsis 组(t=3.471,2.095,P=0.001 3, 0.042 9)。结论 IGF-1R 可通过调控JAK/STAT 信号通路改善脓毒症所致大鼠的肺损伤,降低血清中炎症因子的含量。
Abstract:
Objective To explore the mechanism of insulin-like growth factor 1 receptor (IGF-1R) on sepsis rats by regulating, janus kinase/signal transducer and activvator of transcription (JAK/STAT) signa pathway. Methods Sixty experimental rats were randomly divided into sham operation group(sham group), sepsis rat model group(sepsis group) and sepsis rat model group given IGF-1R intervention group(IGF-1R group), with 20 rats in each group. The proportion of IGF-1R positive cells in rat lung tissue was detected by immunofluorescence staining. The contents of IL-6 and TNF-α in serum were detected by ELISA. The pathological changes of lung tissue were detected by HE staining. Cell apoptosis in each group was detected by TUNEL. The protein expression of p-JAK1 and p-STAT3 in tissues was detected by Western blotting. Results The proportion of IGF-1R positive cells in the sham group (58.32%±5.21%), sepsis group (21.65%±8.73%) and IGF-1R group (46.58%±6.72%) was statistically significant (F=141.7, P<0.000 1).Compared with the sham group, the number of IGF-1R positive cells in the sepsis group was decreased (t=16.13, P<0.000 1), and the number of IGF-1R positive cells in the sepsis group was higher than that in the sepsis group (t=10.12, P<0.000 1), the differences were statistically significant, respectively. The serum IL-6 levels in the sham group (4.35±2.01pg/ml), the sepsis group (9.81±4.26pg/ml) and the IGF-1R group (5.11±2.57pg/ml) were statistically significant different (F=18.23, P<0.000 1). The serum TNF-α levels in the sham group (2.31±1.12pg/ml), sepsis group (14.15±3.26pg/ml) and IGF-1R group (6.58±2.15pg/ml) were significantly different (F=130.7, P<0.000 1). Compared with the sham group, IL-6 and TNF-α increased in the sepsis group (t=5.18, 21.98, all P<0.000 1). The levels of IL-6 and TNF-α in IGF-1R group were lower than those in sepsis group (t=4.23, 12.01, all P<0.000 1). The cell apoptosis rate was significantly different between the sham group (6.35%±2.51%), the sepsis group (37.84±6.62%) and the IGF-1R group (22.71%±4.28%) (F=217.4, P<0.000 1). Compared with the sham group, the apoptosis rate of the sepsis group was increased (t=19.89, P<0.000 1). Compared with the sepsisi group, the percentage of apoptotic cells in the IGF-1R group was lower (t=8.583, P<0.000 1), the differences were statistically significant, respectively. The expression of P-JAK1 in lung tissue showed statistically significant difference in sham group (0.15±0.11), sepsis group (0.33±0.16) and IGF-1R group (0.17±0.13) (F=10.70, P=0.000 1). The expression of p-STAT3 in lung tissue was significantly different in sham group (0.12±0.10), sepsis group (0.28±0.15) and IGF- 1R group (0.19±0.12) (F=8.230, P=0.000 7). Compared with sham group, the expression of p-JAK1 and p-STAT3 proteins increased in sepsis group (t =4.146, 3.969, P =0.000 2, 0.000 3). The protein expressions of p-JAK1 and p-STAT3 in the lung tissues of rats in the IGF-1R group were lower than those in the sepsis group (t =3.471, 2.095, P =0.001 3, 0.042 9). Conclusion IGF-1R can improve the lung injury caused by sepsis by regulating the JAK/STAT signaling pathway and reduce the content of inflammatory factors in serum of rats.

参考文献/References:

[1] 张珍, 王新庄.脓毒症患者血清YKL-40 水平检测与急性肾损伤早期诊断的相关性研究[J].现代检验 医学杂志, 2021, 36(3): 148-150. ZHANG Zhen, WANG Xinzhuang. Correlation between serum YKL-40 level and early diagnosis of acute kidney injury in patients with sepsis [J]. Journal of Modern Laboratory Medicine, 2021, 36(3): 148-150.
[2] MPISANE F, BROOKS A, PERKINS S, et al. Post cardiac surgery sternal wound sepsis burden, risk factors and outcomes at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa: a fiveyear experience[J]. SA Heart, 2020, 17(1):78-89.
[3] GABRIEL V, GRIGORIAN A, NAHMIAS J, et al. Risk factors for Post-Operative sepsis and septic shock in patients undergoing emergency surgery[J]. Surgical Infections(Larchmt), 2019, 20(5): 367-372.
[4] CHANG X, HU L F, MA X J, et al. Influence of roflumilast on sepsis mice through the JAK/STAT signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(3):1335-1341.
[5] CLERE-JEHL R, MARIOTTE A, MEZIANI F, et al. JAK-STAT targeting offers novel therapeutic opportunities in sepsis[J]. Trends in Molecular Medicine, 2020, 26(11): 987-1002.
[6] LIU E H, ZHENG Z N, XIAO C X .IL-22 relieves sepsis-induced liver injury via activating JAK/STAT3 signaling pathway[J]. Journal of Biological Regulators and Homeostatic Agents, 2020, 34(5):1719-1727.
[7] 刘铭传, 李林成, 白晓智. 脓毒症病理生理及信号 转导机制的研究进展[J] . 中华医院感染学杂志, 2019,29(22):3511-3514,3520. LIU Mingchuan, LI Lincheng, BAI Xiaozhi. Progress of study on pathophysiology and signal transduction pathways of sepsis[J]. Chinese Journal of Nosocomiology, 2019, 29 (22): 3511-3514,3520.
[8] 陈爽, 全裕俊, 董蓉, 等. 比较胰岛素样生长因子1 受体抑制剂与胰岛素对2 型糖尿病肾病小鼠肾间 质巨噬细胞浸润的改善作用[J]. 中华肾脏病杂志, 2019, 35(10):765-772. CHEN Shuang, QUAN Yujun, DONG Rong, et al. Comparation of the effects of insulin-like growth factor-1 receptor inhibitor and insulin on renal interstitial macrophage infiltration in mice with type 2 diabetic kidney disease [J]. Chinese Journal of Kidney Disease, 2019, 35(10): 765-772.
[9] HASSANLOU M, SOLTANI B M, MEDLEJ A, et al. Hsa-miR-6165 downregulates insulin-like growth factor-1 receptor (IGF-1R) expression and enhances apoptosis in SW480 cells[J]. Biological Chemistry, 2020, 401(4): 477-485.
[10] 薄禄龙, 邓小明 . 脓毒症的临床与基础研究进展[J]. 国际麻醉学与复苏杂志, 2019, 40(5): 417-419. BO Lulong, DENG Xiaoming. Progress in clinical and basic research of sepsis [J]. International Journal of Anesthesiology and Resuscitation, 2019, 40(5): 417- 419.
[11] 肖武强, 徐敏丹, 吴先正.脓毒症患者血清肠型脂 肪酸结合蛋白、二胺氧化酶水平检测对早期肠组 织损伤及预后的评估价值[J]. 现代检验医学杂志, 2021, 36(1):10-13, 140. XIAO Wuqiang, XU Mindan, WU Xianzheng. Evaluation value of serum intestinal fatty acid binding protein and diamine oxidase in the early stage of intestinal tissue injury and prognosis in patients with sepsis [J]. Journal of Modern Laboratory Medicine, 2021, 36(1) ): 10-13, 140.
[12] 范风江. 脓毒症继发急性肺损伤的临床特征及预后 影响因素分析 [J]. 中国实用医刊, 2021, 48(1): 43-46. FAN Fengjiang. Clinical features and prognostic influencing factors of acute lung injury secondary to sepsis [J]. Chinese Journal of Practical Medicine, 2021, 48(1): 43-46.
[13] 杨阳 , 赵玲 , 杨宗璐 , 等. 胰岛素样生长因子1 在糖 尿病及其并发症中的研究进展[J]. 生物技术通讯, 2020, 31(5): 600-606. YANG Yang, ZHAO Ling, YANG Zonglu, et al. Research progress of IGF-1 in diabetes mellitus and its complications [J]. Letters in Biotechnology , 2020, 31(5): 600-606.
[14] 周虹, 崔娟, 陆尤, 等. 葛瑞林对脓毒症致急性肺损 伤小鼠炎症反应的效果及机制研究[J]. 中日友好医 院学报, 2020,34(2):87-90, 封2. ZHOU Hong, CUI Juan, LU You, et al. Effect and mechanisms of ghrelin on inflammatory responses to sepsis-induced acute lung injury in mice [J]. Journal of China Japan Friendship Hospital, 2020, 34 (2): 87-90, F0002.
[15] 刘继法, 胡渊龙, 邱占军, 等. 中药有效成分治疗脓 毒症急性肺损伤作用机制研究进展[J]. 辽宁中医药 大学学报. 2021,23(1):171-176. LIU Jifa, HU Yuanlong, QIU Zhanjun, et al. Advances in the pathogenesis of active ingredients of traditional Chinese medicine in the treatment of acute lung injury in sepsis [J]. Journal of Liaoning University of Traditional Chinese Medicine, 2021, 23(1): 171-176.
[16] 田杨, 朱翠平, 洪婕, 等. 胰岛素样生长因子-I 和 血糖在脓毒症中的变化及意义[J]. 临床儿科杂志, 2015, 33(6):543-547. TIAN Yang, ZHU Cuiping, HONG Jie, et al. The variation of insulin like growth factor-I and glucose and correlation in children with sepsis [J]. Journal of Clinical Pediatrics, 2015, 33(6): 543-547.
[17] 张淑华, 迟宏罡, 郑学宝.JAK/STAT 信号通路在炎 症性肠病发病机制中的研究进展[J]. 胃肠病学和肝 病学杂志, 2020, 29(3):351-354. ZHANG Shuhua, CHI Honggang, ZHENG Xuebao. Advances of JAK/STAT signaling pathway in the pathogenesis of inflammatory bowel disease [J]. Chinese Journal of Gastroenterology and Hepatology, 2020, 29 (3): 351-354.
[18] 葛改, 杨智雅, 张祥宇, 等.SOCS 通过调控JAK/ STAT 通路影响Th 细胞分化在感染性疾病中的作用 研究进展[J]. 中国真菌学杂志, 2021, 16(1): 51-55. GE Gai, YANG Zhiya, ZHANG Xiangyu, et al. The role of SOCS in Th cell differentiation through JAK / STAT pathway in infectious diseases [J]. Chinese Journal of Mycology, 2021,16 (1): 51-55.
[19] 谢秀芳, 李多, 熊彬, 等. Ghrelin 对脓毒症小鼠肺 脏炎症及JAK/STAT 通路的影响[J]. 国际呼吸杂志, 2016, 36(10):730-734. XIE Xiufang, LI Duo, XIONG Bin, et al. Effects of ghrelinon JAK/STATsignaling in the lung tissues of murine model with sepsis[J]. International Journal of Respiration, 2016, 36 (10): 730-734
[20] XUE Hua, LI Maoxiang. Protective effect of pterostilbene on sepsis-induced acute lung injury in a rat model via the JAK2/STAT3 pathway[J]. Annals of Translational Medicine, 2020, 8(21): 1452.
[21] 谢璨灿, 吴双华, 李峥嵘, 等.电针刺激通过JAK1/ STAT3 通路减轻脓毒症大鼠的急性肺损伤[J]. 南方 医科大学学报,2020,40(11):1662-1667. XIE Cancan, WU Shuanghua, LI Zhengrong, et al. Electroacupuncture protects septic rats from acute lung injury through the JAK1/STAT3 pathway[J]. Journal of Southern Medical University , 2020,40 (11): 1662-1667.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金委员会资助项目(B1702101)。
作者简介:胡伟(1976-),男,大学本科,副主任技师,研究方向:临床检验医学,E-mail:luckycc733@sina.com。
通讯作者:代琼(1966-),女,大学本科,主任技师,研究方向:临床输血,E-mail:371119334@qq.com。
更新日期/Last Update: 1900-01-01