Gemigliptin对野百合碱诱导的肺动脉高压大鼠治疗作用及炎症因子的影响

doi:10.6040/j.issn.1671-7554.0.2016.1300

摘要/Abstract

摘要： 目的观察gemigliptin对野百合碱(MCT)诱导的肺动脉高压大鼠的治疗作用及炎症因子的影响。方法 40只雄性SD大鼠随机分为对照组、MCT诱导的肺动脉高压模型组(MCT组)及gemigliptin干预组(gemigliptin组)。一次性皮下注射MCT(60 mg/kg)分别建立MCT组和gemigliptin组肺动脉高压大鼠模型;同时,gemigliptin组给予gemigliptin灌胃［150 mg/(kg·d)］, 28 d。4周后测平均肺动脉压(mPAP)和肺动脉收缩压(RVSP), 计算右心肥厚指数(RVHI),采用HE 染色法观察肺血管重构情况。采用ELISA法检测大鼠血清中IL-1β和IL-6含量。结果与对照组比较,MCT组mPAP、RVSP明显升高, RVHI显著增加,肺动脉重构显著(P<0.001);gemigliptin组mPAP、RVSP较MCT组显著改善; RVHI明显降低;肺动脉重构情况明显改善(P<0.001)。MCT组白细胞介素-6(IL-6)水平比对照组显著升高(P=0.039), gemigliptin组低于MCT组(P= 0.005); MCT组白细胞介素-1β(IL-1β)水平比对照组显著升高,而gemigliptin组低于MCT组(P<0.001)。结论 gemigliptin可能通过抑制肺血管炎症减缓肺动脉高压的发生发展。

关键词: 野百合碱, gemigliptin, 炎症反应, 白细胞介素-6, 白细胞介素-1β, 肺动脉高压

Abstract: Objective To investigate the effects of gemigliptin on the therapeutic effect and inflammatory factors of monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)in rats. Methods A total of 40 Male SD rats were randomly divided into 3 groups: control group, MCT group and gemigliptin group. The pulmonary hypertension models were established by subcutaneous injection of MCT(60 mg/kg), and rats in the intervention group were treated with gemigliptin［150 mg/(kg·d)］ gavage for 28 days. After that, mean pulmonary artery pressure(mRVP), pulmonary arterial systolic pressure(RVSP), and right ventricular hypertrophy index(RVHI)were measured. The pulmonary vascular remodeling was assessed with HE staining. IL-1β and IL-6 were measured with ELISA. Results The mPAP, RVSP, RVHI and remodeling of the small arteries of the MCT group were significantly improved compared with those of the control group(P<0.001), and those of the gemigliptin group were significantly improved compared with those of the MCT group(P<0.001). The IL-6 level of MCT group was significantly higher than that of the control group(P=0.039), while it was lower of the gemigliptin group than of the MCT group(P=0.005). The IL-1β 山东大学学报 (医学版)55卷5期 -张栾,等.Gemigliptin对野百合碱诱导的肺动脉高压大鼠治疗作用及炎症因子的影响 \=-level of the MCT group was significantly higher than that of the control group, while it was lower of the gemigliptin group than of the MCT group(P<0.001). Conclusion Gemigliptin may reduce the development of pulmonary hypertension by inhibiting pulmonary vascular inflammation.

Key words: Pulmonary arterial hypertension, Monocrotaline, Gemigliptin, Inflammatory reaction, IL-6, IL-1β

中图分类号:

R574

张栾,陈欧,栾云,朱晓波,陈元,王一彪. Gemigliptin对野百合碱诱导的肺动脉高压大鼠治疗作用及炎症因子的影响[J]. 山东大学学报（医学版）, 2017, 55(5): 19-22.

ZHANG Luan, CHEN Ou, LUAN Yun, ZHU Xiaobo, CHEN Yuan, WANG Yibiao. Effects of gemigliptin on the therapeutic effect and inflammatory factors of monocrotaline-induced pulmonary arterial hypertension in rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 19-22.

参考文献

[1] 蒋晓敏, 周陵, 陈绍良. 肺动脉高压肺血管丛状病变的研究进展[J]. 中国病理生理杂志, 2014, 30(8): 1519-1522. JIANG Xiaomin, ZHOU Ling, CHEN Shaoliang. Progress in plexiform lesion of pulmonary hypertension[J]. Chin J Pathophysiology, 2014, 30(8): 1519-1522.
[2] El Chami H, Hassoun PM. Immune and inflammatory mechanisms in pulmonary arterial hypertension[J]. Prog Cardiovasc Dis, 2012, 55(2): 218-228.
[3] Gupta R, Walunj SS, Tokala RK, et al. Emerging drug candidates of dipeptidyl peptidase IV(DPP IV)inhibitor class for the treatment of Type 2 Diabetes[J]. Curr Drug Targets, 2009, 10(1): 71-87.
[4] Hwan HJ, Jung TW, Ryu JY, et al. Dipeptidyl petidase-IV inhibitor(gemigliptin)inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes[J]. Mol Cell Endocrinol, 2014, 392(1-2): 1-7.
[5] Matsuda Y, Hoshikawa Y, Ameshima S, et al. Effects of peroxisome proliferator-activated gamma ligands on monocrotaline-induced pulmonary hypertension in rats[J]. Nihon Kokyuki Gakkai Zasshi, 2005, 43(5): 283-288.
[6] Guignabert C, Tu L, Girerd B, et al. New molecular targets of pulmonary vascular remodeling in pulmonary arterial hypertension importance of endothelial communication[J]. Chest, 2015, 147(2): 529-537.
[7] Montani D, Chaumais MC, Guignabert C, et al. Targeted therapies in pulmonary arterial hypertension[J]. Pharmacol Ther, 2014, 141(2): 172-191.
[8] Rabinovitch M, Guignabert C, Humbert M, et al. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension[J]. Circ Res, 2014, 115(1): 165-175.
[9] Huertas A, Perros F, Tu L, et al. Immune dysregulation and endothelial dysfunction in pulmonary arterial hypertension a complex interplay[J]. Circulation, 2014, 129(12): 1332-1340.
[10] Tanino Y. Monocrotaline-induced pulmonary hypertension in animals[J]. Nihon Rinsho, 2001, 59(6): 1076-1080.
[11] Price LC, Wort SJ, Perros F, et al. Inflammation in pulmonary arterial hypertension[J]. Chest, 2012, 141(1): 210-221.
[12] Bi LQ, Zhu R, Kong H, et al. Ruscogenin attenuates monocrotaline-induced pulmonary hypertension in rats[J]. Int Immunopharmacol, 2013, 16(1): 7-16.
[13] Tian W, Jiang X, Sung YK, et al. Leukotrienes in pulmonary arteria hypertension[J]. Immunol Res, 2014, 58(2-3): 387-393.
[14] Meloche J, Renard S, Provencher S, et al. Anti-inflammatory and immunosuppressive agents in PAH[J]. Handb Exp Pharmacol, 2013, 218: 437-476.
[15] Secher A, Jelsing J, Baquero AF, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss[J]. J Clin Invest, 2014, 124(10): 4473-4488.
[16] Zhong J, Rao X, Rajagopalan S. An emerging role of dipeptidyl peptidase 4(DPP4)beyond glucose control: potential implications in cardiovascular disease[J]. Atherosclerosis, 2013, 226(2): 305-314.
[17] Zhong J, Rao X, Deiuliis J, et al. A potential role for dendritic cell/macrophage-expressing DPP4 in obesity-induced visceral inflammation[J]. Diabetes, 2013, 62(1): 149-157.
[18] Ta NN, Schuyler CA, Li Y, et al. DPP-4(CD26)inhibitor alogliptin inhibits atherosclerosis in diabetic apolipoprotein E-deficient mice[J]. J Cardiovasc Pharmacol, 2011, 58(2): 157-166.
[19] Shirakawa J, Fujii H, Ohnuma K, et al. Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice[J]. Diabetes, 2011, 60(4): 1246-1257.
[20] Reinhold D, Bank U, Bühling V, et al. Dipeptidyl peptidase IV(CD26)on human lymphocytes. Synthetic inhibitors of and antibodies against dipeptidyl peptidase IV suppress the proliferation of pokeweed mitogen-stimulated peripheral blood mononuclear cells, and IL-2 and IL-6 production[J]. Immunobiology, 1993, 188(4-5): 403-414.
[21] Choi SH, Park S, Oh CJ, et al. Dipeptidyl peptidase-4 inhibition by gemigliptin prevents abnormal vascular remodeling via NF-E2-related factor 2 activation[J]. Vascul Pharmacol, 2015, 73: 11-19. doi: 10.1016/j.vph.2015.07.005.
[22] Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease[J]. Cell, 2010, 140(6): 900-917.

相关文章 15

[1]	贾若曦,吕丽,刘涵云,吴寅平,李凤彩,赵泽华,王凯,范玉琛. 血细胞计数相关标志物对慢加急性乙型肝炎肝衰竭患者28天预后的诊断价值[J]. 山东大学学报 (医学版), 2025, 63(6): 89-99.
[2]	杜艾家,张曼,陈鹤,王丽新,尚应殊. 微小RNA-1270靶向调控血管生成素样蛋白7抑制巨噬细胞炎症和脂质蓄积[J]. 山东大学学报 (医学版), 2025, 63(2): 1-9.
[3]	赵子辉,王旭阳,张鹏,方宁宁,石端博,杨帆,杨晓玫,吴剑波. 经膈肌穿刺法快速准确评估大鼠肺动脉高压[J]. 山东大学学报 (医学版), 2024, 62(2): 20-28.
[4]	杨元凤,熊高才,黎豫川,罗玉玲,张敬杰. 鹿苓安肾颗粒对慢性肾功能衰竭大鼠炎症反应及细胞凋亡的影响[J]. 山东大学学报 (医学版), 2023, 61(10): 9-16.
[5]	李锐,石存现,于翠翠. 右美托咪定对30例体外循环患者肠道屏障损伤的影响[J]. 山东大学学报 (医学版), 2022, 60(7): 83-88.
[6]	曾媛媛,杨东鹏,董柱,张本,曹一秋,王晓武. 川芎嗪对野百合碱诱导大鼠肺动脉高压的影响及机制[J]. 山东大学学报 (医学版), 2022, 60(11): 63-69.
[7]	周溪,黄霂晗,任玉洁,邱洋. 新型冠状病毒感染与天然免疫及炎症反应[J]. 山东大学学报 (医学版), 2021, 59(5): 15-21.
[8]	闵傲雪,朱天瑞,张凤,王冉冉,李晓红. A151对糖氧剥夺和脂多糖诱导的BV-2细胞极化的影响[J]. 山东大学学报 (医学版), 2021, 59(3): 1-9.
[9]	杨佳,张曼,陈凯明,曹曦. miR-146a经TLR4/MyD88途径加速巨噬细胞迁移所致动脉硬化的作用机制[J]. 山东大学学报 (医学版), 2021, 59(11): 1-7.
[10]	高金梅,黄映波,冯珍珍. 单核细胞趋化蛋白-1对67例全身炎症反应综合征患者的诊断价值[J]. 山东大学学报 (医学版), 2021, 59(10): 77-81.
[11]	安袁笑雪,赵玉英,赵翠芬,许瑞英,薛玉文. 合并型甲基丙二酸血症并发肺动脉高压2例并文献复习[J]. 山东大学学报 (医学版), 2021, 59(10): 103-109.
[12]	王波,薛江,刘爱虹,翟蕊蕊,王一彪. 雷帕霉素调控巨噬细胞表型改善肺动脉高压[J]. 山东大学学报 (医学版), 2018, 56(4): 51-57.
[13]	郭配,李秀华,张晓韬,何天齐,朱梅佳,唐吉友,赵张宁,毛飞. 伴有睡眠障碍帕金森病患者的睡眠特征及其影响因素[J]. 山东大学学报 (医学版), 2018, 56(4): 76-80.
[14]	陈攀,蒋春霞,雷艺. 2型糖尿病患者外周血突触融合蛋白8表达与慢性炎症、糖脂代谢的相关性[J]. 山东大学学报 (医学版), 2018, 56(12): 26-32.
[15]	许天一,吴萍,王爱玲,陈丽萍. 米力农雾化治疗小儿重症肺炎合并心力衰竭的疗效[J]. 山东大学学报（医学版）, 2016, 54(7): 88-90.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed