三七总皂苷对肺动脉高压大鼠肺血管重构的影响及其机制*

doi:10.12047/j.cjap.6358.2022.118

摘要/Abstract

摘要： 目的: 探讨三七总皂苷(PNS)对肺动脉高压(PAH)大鼠肺血管重构及SIRT1/FOXO3a/p27通路的影响。方法: 将体重200~250 g雄性SD大鼠随机分为对照组(Control),野百合碱组(MCT),野百合碱+三七总皂苷组(MCT+PNS),每组各10只。Control组:第1日腹腔注射生理盐水3 ml/kg,随后每天腹腔注射生理盐水2.5 ml/kg;MCT组:第1日腹腔注射MCT 60 mg/kg,随后每天注射2.5 ml/kg 生理盐水;MCT+PNS组:第1日腹腔注射MCT 60 mg/kg,随后每天腹腔注射PNS 50 mg/kg,常规饲养4周。造模完成后,采用右心导管法检测各组大鼠平均肺动脉压(mPAP)、右心室收缩压(RVSP),称重并计算右心室肥厚指数(RVHI),HE和Masson染色观察肺血管结构和形态变化,qPCR和Western blot检测SIRT1、FOXO3a、p27、PCNA和Caspase-3的蛋白和基因层面的表达变化。结果: 与Control组相比,MCT组mPAP、RVSP和RVHI均显著上升(P＜0.01),肺血管明显增厚以及胶原纤维增多,SIRT1、FOXO3a、p27和Caspase-3蛋白和基因表达均下降(P＜0.05或P＜0.01),PCNA蛋白和基因表达均增多(P＜0.05);与MCT组相比,MCT+PNS组mPAP、RVSP和RVHI显著下降(P＜0.05或P＜0.01),肺血管增厚得到改善以及胶原纤维减少,SIRT1、FOXO3a、p27和Caspase-3蛋白和基因表达均增多(P＜0.05或P＜0.01),PCNA蛋白和基因表达均降低(P＜0.05或P＜0.01)。结论: 三七总皂苷可通过激活SIRT1/FOXO3a/p27通路缓解肺动脉高压大鼠的肺血管重构。

关键词: 三七总皂苷, 肺动脉高压, SIRT1/FOXO3a/p27通路, 野百合碱, 大鼠

Abstract: Objective: To investigate the effects of panax notoginseng saponins (PNS) on pulmonary vascular remodeling and SIRT1/FOXO3a/p27 pathway in pulmonary arterial hypertension (PAH) rats. Methods: Male SD rats weighing 200~250g were randomly divided into control group, monocrotaline group (MCT) and monocrotaline + panax notoginseng saponins group (MCT+PNS), with 10 rats in each group. The rats in control group were injected intraperitoneally with normal saline 3 ml/kg on the first day, then injected intraperitoneally with normal saline 2.5 ml/kg every day. The rats in MCT group were injected intraperitoneally with MCT 60 mg/kg on the first day, followed by daily injection of normal saline 2.5 ml/kg. In MCT+PNS group, 60 mg/kg MCT was injected intraperitoneally on the first day, and 50 mg/kg PNS was injected intraperitoneally every day. The above models were fed conventionally for 4 weeks. After the modeling was completed, the mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) of rats in each group were detected by right heart catheter method, weighed and calculated right ventricular hypertrophy index (RVHI), and the pulmonary vascular structure and morphological changes were observed by HE and Masson staining. The protein and gene expressions of SIRT1, FOXO3a, p27, PCNA and Caspase-3 were detected by qPCR and Western blot. Results: Compared with control group, mPAP, RVSP and RVHI in MCT group were increased significantly (P＜0.01), pulmonary vessels were thickened significantly and collagen fibers were increased, protein and gene expressions of SIRT1, FOXO3a, p27 and Caspase-3 were decreased (P＜0.05 or P＜0.01). The protein and gene expressions of PCNA were increased (P＜0.05). Compared with MCT group, the levels of mPAP, RVSP and RVHI in MCT+PNS group were decreased significantly (P＜0.05 or P＜0.01), pulmonary vascular thickening was alleviated and collagen fibers were reduced. The protein and gene expressions of SIRT1, FOXO3a, p27 and Caspase-3 were increased (P＜0.05 or P＜0.01), while the protein and gene expressions of PCNA were decreased (P＜0.05 or P＜0.01). Conclusion: Panax notoginseng saponins can relieve pulmonary vascular remodeling in rats with pulmonary hypertension by activating SIRT1/FOXO3a/p27 pathway.

Key words: Panax notoginseng saponins, pulmonary arterial hypertension, SIRT1 / FOXO3a/p27 pathway, monocrotaline, rats

中图分类号:

R285.5

宋正阳, 王新雨, 田云娜, 李卓伦, 王肖婷, 袁琳波, 王万铁. 三七总皂苷对肺动脉高压大鼠肺血管重构的影响及其机制^*[J]. 中国应用生理学杂志, 2022, 38(6): 650-654.

SONG Zheng-yang, WANG Xin-yu, TIAN Yun-na, LI Zhuo-lun, WANG Xiao-ting, YUAN Lin-bo, WANG Wan-tie. Effects of panax notoginseng saponins on pulmonary vascular remodeling in rats with pulmonary hypertension and its mechanisms[J]. CJAP, 2022, 38(6): 650-654.

参考文献

[1] Lau EMT, Giannoulatou E, Celermajer DS, et al. Epidemiology and treatment of pulmonary arterial hypertension [J]. Nat Rev Cardiol, 2017, 14(10): 603-614.
[2] Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: The joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT) [J]. Eur Heart J, 2016, 37(1): 67-119.
[3] Xiao Y, Chen PP, Zhou RL, et al. Pathological mechanisms and potential therapeutic targets of pulmonary arterial hypertension: A review [J]. Aging Dis, 2020, 11(6): 1623-1639.
[4] Stewart S, Strange GA, Playford D. The challenge of an expanded therapeutic window in pulmonary hypertension [J]. Nat Rev Cardiol, 2020, 17(4): 195-197.
[5] Kudryashova TV, Goncharov DA, Pena A, et al. HIPPO-integrin-linked kinase cross-talk controls self-sustaining proliferation and survival in pulmonary hypertension[J]. Am J Respir Crit Care Med, 2016, 194(7): 866-877.
[6] 蒋赛, 彭晓珊, 黄志华, 等. 黄芪多糖和三七总皂苷配伍对糖尿病大鼠肾组织Ⅳ型胶原及层黏连蛋白表达的影响 [J]. 湖南中医药大学学报, 2015, 35(12): 18-22.
[7] 杨小晖, 黄鹏, 罗金文. 三七总皂甙对肺动脉高压大鼠肺动脉病理的影响 [J]. 中国医师杂志, 2015, 17(10): 1532-1535.
[8] Rajendrasozhan S, Yang SR, Kinnula VL, et al. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease [J]. Am J Respir Crit Care Med, 2008, 177(8): 861-870.
[9] Chen B, Xue J, Meng X, et al. Resveratrol prevents hypoxia-induced arginase II expression and proliferation of human pulmonary artery smooth muscle cells via Akt-dependent signaling [J]. Am J Physiol Lung Cell Mol Physiol, 2014, 307(4): L317-L325.
[10] Yamamoto M, Kondo E, Takeuchi M, et al. miR-155, a modulator of FOXO3a protein expression, is underexpressed and cannot be upregulated by stimulation of HOZOT, a line of multifunctional Treg [J]. PLoS One, 2011, 6(2): e16841.
[11] 朱阿楠, 王园园, 王淑君, 等. ERK通路和三七总皂苷干预在低氧高二氧化碳性肺动脉高压中的作用 [J]. 中国病理生理杂志, 2011, 27(9): 1796-1801.
[12] Dignam JP, Scott TE, Kemp-Harper BK, et al. Animal models of pulmonary hypertension: Getting to the heart of the problem [J]. Br J Pharmacol, 2022, 179(5): 811-837.
[13] 张赛, 宋正阳, 王淑远, 等. 三七总皂苷通过Notch3/Hes-1/p27~(Kip1)信号通路抑制低氧性肺动脉高压大鼠肺血管重构 [J]. 中国病理生理杂志, 2022, 38(2): 209-214.
[14] Chung S, Yao H, Caito S, et al. Regulation of SIRT1 in cellular functions: role of polyphenols [J]. Arch Biochem Biophys, 2010, 501(1): 79-90.
[15] Donmez G, Guarente L. Aging and disease: connections to sirtuins [J]. Aging Cell, 2010, 9(2): 285-290.
[16] Zhang J, Lee SM, Shannon S, et al. The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice [J]. J Clin Invest, 2009, 119(10): 3048-3058.
[17] Dang W, Steffen KK, Perry R, et al. Histone H4 lysine 16 acetylation regulates cellular lifespan [J]. Nature, 2009, 459(7248): 802-807.
[18] Willcox BJ, Donlon TA, He Q, et al. FOXO3A genotype is strongly associated with human longevity [J]. Proc Natl Acad Sci U S A, 2008, 105(37): 13987-13992.
[19] Sengupta A, Molkentin JD, Paik JH, et al. FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress [J]. J Biol Chem, 2011, 286(9): 7468-7478.
[20] Shrestha A, Nepal S, Kim MJ, et al. Critical role of AMPK/FoxO3A axis in globular adiponectin-induced cell cycle arrest and apoptosis in cancer cells[J]. J Cell Physiol, 2016, 231(2): 357-369.
[21] Zurlo G, Piquereau J, Moulin M, et al. Sirtuin 1 regulates pulmonary artery smooth muscle cell proliferation: role in pulmonary arterial hypertension [J]. J Hypertens, 2018, 36(5): 1164-1177.
[22] Bo Y, Jian Z, Zhi-Jun S, et al. Panax notoginseng saponins alleviates advanced glycation end product-induced apoptosis by upregulating SIRT1 and antioxidant expression levels in HUVECs [J]. Exp Ther Med, 2020, 20(5): 99.
[23] Du YG, Wang LP, Qian JW, et al. Panax notoginseng saponins protect kidney from diabetes by up-regulating silent information regulator 1 and activating antioxidant proteins in rats [J]. Chin J Integr Med, 2016, 22(12): 910-917.

三七总皂苷对肺动脉高压大鼠肺血管重构的影响及其机制^*

Effects of panax notoginseng saponins on pulmonary vascular remodeling in rats with pulmonary hypertension and its mechanisms

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