消痰化瘀利窍方对慢性间歇性低氧大鼠肠系膜动脉损伤的改善作用*

doi:10.12047/j.cjap.5725.2019.044

摘要/Abstract

摘要： 目的:观察消痰化瘀利窍方对慢性间歇性低氧(CIH)大鼠肠系膜动脉功能损伤的作用,并探讨其可能机制。方法:48只雄性SD大鼠随机分为4组(n=12),常氧对照组(Normoxia)、慢性间歇性低氧组(CIH)、慢性间歇性低氧中药干预组(Formula+CIH)、中药对照组(Formula)。CIH与Formula+CIH组置于间歇性低氧装置,通过充入氮气、氧气使O₂含量在9%至21%间循环,每循环3 min;Normoxia和Formula组则充入空气。其中,Formula +CIH与Formula组于每日造模前中药水煎液灌胃(24 g/kg),而CIH组与Normoxia组给予等量生理盐水。造模结束后,应用HE染色观察各组大鼠肠系膜动脉的组织病理学改变,通过微血管环技术观察ACh、L-Arg诱导的肠系膜动脉舒张反应,通过ELISA技术检测大鼠造模前及造模21 d血清一氧化氮(NO)的含量并应用Western blot技术测定肠系膜动脉eNOS和p-eNOS的蛋白水平。结果:与Normoxia组相比,CIH组大鼠肠系膜动脉内皮明显损伤、中膜增厚,ACh、L-Arg诱导的肠系膜动脉舒张反应明显减弱,血清中NO水平及肠系膜动脉p-eNOS/eNOS比值显著降低。消痰化瘀利窍方干预能够减轻大鼠肠系膜动脉的内膜与中膜病理损伤,改善肠系膜动脉舒张功能,提高血清NO含量及肠系膜动脉eNOS磷酸化水平。而单纯给予消痰化瘀利窍方大鼠与Normoxia组相比各指标均未发现显著变化。结论:消痰化瘀利窍方可以减轻慢性间歇性低氧引起的大鼠肠系膜动脉功能损伤,其机制与提高NO的生物利用度有关。

关键词: 消痰化瘀利窍方, 慢性间歇性低氧, 肠系膜动脉, 内皮功能障碍, 一氧化氮, 大鼠

Abstract: Objective: To investigate the effects of Xiaotan Huayu Liqiao formula (the Chinese Medicine) on mesenteric artery function in rats exposed to chronic intermittent hypoxia (CIH), and to explore the related mechanism. Methods: Forty-eight male SD rats were randomly divided into four groups as Normoxia, CIH, Formula+CIH and formula group. Rats were exposed to normoxia in the Normoxia and Formula group, or intermittent hypoxia in CIH or Formula+CIH group. Xiaotan Huayu Liqiao formula was given at 24g/kg by intragastric administration before intermittent hypoxia exposure. The pathological changes of mesenteric artery were determined by HE staining, and the relaxation of mesenteric artery (induced by acetylcholine(ACh) and L-arginine(L-Arg)) was recorded by microvascular ring technique. Serums of all rats were collected (0 d and 21 d) and the content of NO was detected by ELISA. The levels of endothelial nitric oxide synthase (eNOS) and p-eNOS were measured by Western blot. Results: Compared with Normoxia group, the mesenteric arterial endothelial injury and media thickening were observed and the relaxation of mesenteric artery was significantly reduced in rats exposed to CIH. The level of NO in serum and the ratio of p-eNOS/eNOS were also decreased in the CIH group. Xiaotan Huayu Liqiao formula administration improved the pathologic changes and dilatation function of mesenteric artery, increased the levels of NO and p-eNOS. Compared with Normoxia group,all the results were not observed significant difference in Formula group. Conclusion: Xiaotan Huayu Liqiao formula increased the bioavailability of NO, and ameliorated the CIH induced mesenteric artery function injury.

Key words: chronic intermittent hypoxia, mesenteric artery, endothelial dysfunction, nitric oxide, Xiaotan Huayu Liqiao formula, rat

于富洋, 杨胜昌, 郭亚净, 赵亚硕, 刘思文, 吉恩生. 消痰化瘀利窍方对慢性间歇性低氧大鼠肠系膜动脉损伤的改善作用^*[J]. 中国应用生理学杂志, 2019, 35(3): 204-208.

YU Fu-yang, YANG Sheng-chang, GUO Ya-jing, ZHAO Ya-shuo, LIU Si-wen, JI En-sheng. The effects of Xiaotan Huayu Liqiao formula on mesenteric artery function in rats exposed to chronic intermittent hypoxia[J]. CJAP, 2019, 35(3): 204-208.

参考文献

[1] Punjabi NM. The epidemiology of adult obstructive sleep apnea[J]. Proc Am Thorac Soc, 2008, 5(2): 136-143.
[2] Badran M, Ayas N, Laher I. Insights into obstructive sleep apnea research[J]. Sleep Med, 2014, 15(5): 485-495.
[3] Ramar K, Caples SM. Cardiovascular consequences of obese and nonobese obstructive sleep apnea[J]. Med Clin North Am, 2010, 94(3): 465-478.
[4] Kohler M, Stradling JR. Mechanisms of vascular damage in obstructive sleep apnea[J]. Nat Rev Cardiol, 2010, 7(12): 677-685.
[5] Maeder MT, Schoch OD, Rickli H. A clinical approach to obstructive sleep apnea as a risk factor for cardiovascular disease[J]. Vasc Health Risk Manag, 2016, 12: 85-103.
[6] Buchner NJ, Quack I, Woznowski M, et al. Microvascular endothelial dysfunction in obstructive sleep apnea is caused by oxidative stress and improved by continuous positive airway pressure therapy[J]. Respiration, 2011, 82(5): 409-417.
[7] 李浩, 张苏丽, 杨艳,等. 利用微血管环技术检测肠系膜动脉三级分支张力的方法[J]. 中国应用生理学杂志, 2014, 30(3): 214-217.
[8] Jafari B, Mohsenin V. Chitinase-3-like protein-1 (YKL-40) as a marker of endothelial dysfunction in obstructive sleep apnea[J]. Sleep Med, 2016, 25: 87-92.
[9] Chen L, Guo QH, Chang Y, et al. Tanshinone IIA ameliorated endothelial dysfunction in rats with chronic intermittent hypoxia[J]. Cardiovasc Pathol, 2017, 31: 47-53.
[10]Duchna HW, Guilleminault C, Stoohs RA, et al. Vascular reactivity in obstructive sleep apnea syndrome[J]. Am J Respir Crit Care Med, 2000, 161(1): 187-191.
[11]Kato M, Roberts-Thomson P, Phillips BG, et al. Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea[J]. Circulation, 2000, 102(21): 2607-2610.
[12]明佳, 徐竞, 李涛, 等. 连接蛋白40/43调节大鼠血管平滑肌细胞内钙离子浓度与肠系膜上动脉收缩反应性的研究[J]. 中华烧伤杂志, 2009, 25(1): 31-35.
[13]Ayas NT, Taylor CM, Laher I. Cardiovascular consequences of obstructive sleep apnea[J]. Curr Opin Cardiol, 2016, 31(6): 599-605.
[14]Krause BJ, del Rio R, Moya EA, et al. Arginase-endothelial nitric oxide synthase imbalance contributes to endothelial dysfunction during chronic intermittent hypoxia[J]. J Hypertens, 2015, 33(3): 515-524.
[15]Delaey C, Boussery K, van de Voorde J. Contractility studies on isolated bovine choroidal small arteries: determination of the active and passive wall tension-internal circumference relation[J]. Exp Eye Res, 2002, 75(3): 243-248.
[16]Saletu M, Sauter C, Lalouschek W, et al. Is excessive daytime sleepiness a predictor of carotid atherosclerosis in sleep apnea[J]? Atherosclerosis, 2008, 196(2): 810-816.
[17]Guo QH, Tian YL, Wang Z, et al. Endothelin receptors in augmented vasoconstrictor responses to endothelin-1 in chronic intermittent hypoxia[J]. Clin Exp Pharmacol Physiol, 2013, 40(7): 449-457.
[18]Wang JW, Li AY, Guo QH, et al. Endothelin-1 and ET receptors impair left ventricular function by mediated coronary arteries dysfunction in chronic intermittent hypoxia rats[J]. Physiol Rep, 2017, 5(1): e13050.
[19]杨玉萍, 李瑞旻, 李佳佳, 等. 阻塞性睡眠呼吸暂停低通气综合征合并高血压中医分型与睡眠参数的相关性研究[J]. 江西中医药, 2018, 49(3): 38-41.
[20]Grossini E, Gramaglia C, Farruggio S, et al. Asenapine increases nitric oxide release and protects porcine coronary artery endothelial cells against peroxidation[J]. Vascul Pharmacol, 2014, 60(3): 127-141.
[21]Umans JG, Levi R. Nitric oxide in the regulation of blood flow and arterial pressure[J]. Annu Rev Physiol, 1995, 57: 771-790.
[22]赵艳霞, 李玉红, 王亚平, 等. 高脂饮食对慢性低氧大鼠肺组织 eNOS /NO 的影响[J]. 中国应用生理学杂志, 2014, 30(4): 377-380.
[23]Lavie L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia--revisited--the bad ugly and good: implications to the heart and brain[J]. Sleep Med Rev, 2015, 20: 27-45.
[24]Yu FC, Yuan CX, Tong JY, et al. Protective effect of sphingosine-1-phosphate for chronic intermittent hypoxia-induced endothelial cell injury[J]. Biochem Biophys Res Commun, 2018, 498(4): 1016-1021.
[25]Hernandez-Guerra M, De Ganzo ZA, Gonzalez-Mendez Y, et al. Chronic intermittent hypoxia aggravates intrahepatic endothelial dysfunction in cirrhotic rats[J]. Hepatology, 2013, 57(4): 1564-1574.
[26]Montanez R, Rodriguez-Caso C, Sanchez-Jimenez F, et al. In silico analysis of arginine catabolism as a source of nitric oxide or polyamines in endothelial cells[J]. Amino Acids, 2008, 34(2): 223-229.
[27]Santhanam L, Christianson DW, Nyhan D, et al. Arginase and vascular aging[J]. J Appl Physiol (1985), 2008, 105(5): 1632-1642.
[28]Krause BJ, Carrasco-Wong I, Caniuguir A, et al. Endothelial eNOS/arginase imbalance contributes to vascular dysfunction in IUGR umbilical and placental vessels[J]. Placenta, 2013, 34(1): 20-28.
[29]Demougeot C, Prigent-Tessier A, Marie C, et al. Arginase inhibition reduces endothelial dysfunction and blood pressure rising in spontaneously hypertensive rats[J]. J Hypertens, 2005, 23(5): 971-978.

消痰化瘀利窍方对慢性间歇性低氧大鼠肠系膜动脉损伤的改善作用^*

The effects of Xiaotan Huayu Liqiao formula on mesenteric artery function in rats exposed to chronic intermittent hypoxia

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	扈敬, 李法东, 邵小婷, 李思葳, 张欣颖, 赵冰冰, 徐长庆, 魏璨. 精胺对高糖引起的大鼠心肌纤维化的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 193-196.
[2]	朱建忠, 赵灿, 隋月林, 刘媛媛, 乔跃兵. 瘦素对糖尿病大鼠糖脂代谢及炎性因子的影响[J]. 中国应用生理学杂志, 2020, 36(3): 197-201.
[3]	孙晓娟, 冯武龙, 侯娜, 李娜, 姜蔚丽. 有氧运动和白藜芦醇对2型糖尿病大鼠肾脏JAK2及TGF-β1的影响[J]. 中国应用生理学杂志, 2020, 36(3): 202-206.
[4]	石慧, 梁晓珊, 黄丽文, 罗之刚, 谭龙. 一种高尿酸血症大鼠模型诱导方法的改良和效果评价研究[J]. 中国应用生理学杂志, 2020, 36(3): 223-227.
[5]	杨琼, 潘娅, 陈粲, 戴桃李. 阿尼西坦对血管性痴呆大鼠的治疗作用[J]. 中国应用生理学杂志, 2020, 36(3): 232-234.
[6]	韩洁, 刘子怡, 方振, 田蕾, 杨丹凤, 袭著革, 刘晓华. 重复制动应激对雌性大鼠下丘脑-垂体-卵巢轴的影响[J]. 中国应用生理学杂志, 2020, 36(3): 245-249.
[7]	孙景然, 樊祢祢, 张桢, 吴瑾, 韩殿鹏, 白家磊, 杜连群, 房彦军. 有机磷阻燃剂TDCIPP对雌性大鼠甲状腺的潜在毒性作用[J]. 中国应用生理学杂志, 2020, 36(3): 250-254.
[8]	陈宇峰, 董凡赫, 楼云玮, 寿今豪, 张慧婷, 周一超, 严明, 毛红娇, 张云. 补骨脂素对TCP磨损颗粒所致大鼠成骨细胞损伤的干预作用及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 255-260.
[9]	李家卉, 张敏, 付子豪, 李勇枝, 王佳平, 高峰, 董玲. 经皮穿刺抽取大鼠脑脊液方法的改良[J]. 中国应用生理学杂志, 2020, 36(3): 265-267.
[10]	徐昌顺, 孙培, 林春. 改良型大鼠鞘内穿刺置管针及导管末端注药装置在大鼠鞘内置管术中的应用研究[J]. 中国应用生理学杂志, 2020, 36(3): 283-288.
[11]	王凌星, 洪姗燕, 杨美丽, 黄红红. 丁苯酞对睡眠剥夺大鼠额叶小胶质细胞活化的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 106-110.
[12]	完建永, 张勇, 刘世强, 华田苗, 孙庆艳. 运动对胰岛素抵抗大鼠肝脏BIM信号通路的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 115-118.
[13]	姚良雪, 韩家鑫, 魏培韵, 侯思博, 何潇剑, 张瑞岭, 杜爱林. 丁苯酞对慢性酒精中毒大鼠海马、杏仁核H₂S/CBS通路及学习记忆能力的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 138-142.
[14]	赵洋, 杨胜昌, 于富洋, 李文雅, 吉恩生. 消痰化瘀利窍方对慢性间歇性低氧小鼠认知障碍的改善作用^*[J]. 中国应用生理学杂志, 2020, 36(2): 143-147.
[15]	窦丽. 游泳训练对高血压大鼠血压及血栓前状态分子的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 161-164.