丁酸通过激活G蛋白偶联受体41/43通路降低高血压大鼠血压

doi:10.11958/20221713

天津医药 ›› 2023, Vol. 51 ›› Issue (9): 972-976.doi: 10.11958/20221713

丁酸通过激活G蛋白偶联受体41/43通路降低高血压大鼠血压

秦春迪(), 马雯, 李圆, 朱雅泉, 李瑜, 邹琳, 张昕^△()

内蒙古科技大学包头医学院第一附属医院心内科（邮编014010）

收稿日期:2022-10-27 修回日期:2023-01-31 出版日期:2023-09-15 发布日期:2023-09-13
通讯作者: △E-mail：zhangxinwdq@sina.com
作者简介:秦春迪（1987），女，硕士在读，主要从事心血管病方面研究。E-mail：zhiyou_13@126.com

Butyrate reduces blood pressure in hypertensive rats by activating the G protein-coupled receptor 41/43 pathway

QIN Chundi(), MA Wen, LI Yuan, ZHU Yaquan, LI Yu, ZOU Lin, ZHANG Xin^△()

Department of Cardiology, the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014010, China

Received:2022-10-27 Revised:2023-01-31 Published:2023-09-15 Online:2023-09-13
Contact: △E-mail：zhangxinwdq@sina.com

秦春迪, 马雯, 李圆, 朱雅泉, 李瑜, 邹琳, 张昕. 丁酸通过激活G蛋白偶联受体41/43通路降低高血压大鼠血压[J]. 天津医药, 2023, 51(9): 972-976.

QIN Chundi, MA Wen, LI Yuan, ZHU Yaquan, LI Yu, ZOU Lin, ZHANG Xin. Butyrate reduces blood pressure in hypertensive rats by activating the G protein-coupled receptor 41/43 pathway[J]. Tianjin Medical Journal, 2023, 51(9): 972-976.

摘要/Abstract

摘要：

目的探讨丁酸通过激活G蛋白偶联受体41/43（GPR41/43）通路降低高血压模型大鼠血压的机制。方法 75只雄性SD大鼠随机分为假手术组（15只）和造模组（60只），采用两肾一夹方法建立高血压大鼠模型，将成模鼠随机分为对照组（超纯水0.1 mL/kg）、丁酸高剂量组（220 mg/kg）、丁酸低剂量组（110 mg/kg）和缬沙坦组（30 mg/kg），每组15只，连续灌胃给药4周。分别在给药前后测量大鼠尾动脉收缩压（SBP）及心率（HR）。采用酶联免疫吸附试验（ELISA）检测大鼠血清中白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）及内皮型一氧化氮合酶（eNOS）含量；实时荧光定量PCR（qPCR）检测大鼠胸主动脉组织中IL-6、TNF-α、eNOS的mRNA表达水平。免疫组织化学染色检测大鼠胸主动脉GPR41/43表达量。结果给药2周，对照组大鼠SBP较假手术组显著升高（P<0.05），丁酸高剂量组、丁酸低剂量组、缬沙坦组SBP较对照组降低，且丁酸高剂量组低于低剂量组（P<0.05）。给药4周，丁酸高剂量组较丁酸低剂量组SBP明显降低（P<0.05）；给药前后各组大鼠HR差异均无统计学意义（P>0.05）。给药后丁酸高剂量组、丁酸低剂量组eNOS蛋白和mRNA表达量较对照组增加，IL-6、TNF-α蛋白及mRNA表达量均降低（P<0.05）。免疫组织化学染色显示，大鼠胸主动脉组织的GPR41/43表达较对照组增加，且高于缬沙坦组（P<0.05）。结论丁酸对高血压大鼠有明显的降压作用，可能与激活GPR41/43通路增加血管舒张，抑制炎性因子表达有关。

关键词: 丁酸盐类, 高血压, 受体, G-蛋白偶联, 白细胞介素6, 肿瘤坏死因子α, 一氧化氮合酶Ⅲ型

Abstract:

Objective To investigate the mechanism of butyrate reducing blood pressure in hypertensive model rats by activating G protein-coupled receptor 41/43 (GPR41/43) pathway. Methods Seventy-five male SD rats were randomly divided into the sham operation group (n=15) and the model group (n=60). Hypertensive rat model was established by two kidneys and one clip method. Model rats were randomly divided into the control group (0.1 mL/kg ultra-pure water), the butyrate high-dose group (220 mg/kg), the butyrate low-dose group (110 mg/kg) and the valsartan group (30 mg/kg), with 15 rats in each group. Rats were given intervention by cntinuous gavage for 4 weeks. Caudal artery systolic blood pressure (SBP) and heart rate (HR) were measured before and after administration. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and endothelial nitric oxide synthase (eNOS) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of IL-6, TNF-α and eNOS in thoracic aorta were detected by real-time fluorescent quantitative PCR (qPCR). The expression of GPR41/43 in rat thoracic aorta was detected by immunohistochemistry. Results After 2 weeks of administration, SBP was significantly higher in the control group than that in the sham operation group (P<0.05). Values of SBP were significantly lower in the high dose butyrate group, the low dose butyrate group and the valsartan group than those in the control group, and SBP was significantly lower in the butyrate high dose group than that of the butyrate low dose group (P<0.05). After 4 weeks of administration, SBP was significantly lower in the high dose group than that in the low dose group (P<0.05). There were no significant differences in HR before and after administration between groups (P>0.05). After administration, the protein expression and mRNA expression of eNOS were increased in the butyrate high dose group and the butyrate low dose group compared with those of the control group, and the protein expression and mRNA expression of IL-6 and TNF-α were decreased (P<0.05). Immunohistochemistry showed that the expression of GPR41/43 in rat thoracic aorta tissue was increased compared with that of the control group, and which was higher than that in the valsartan group (P<0.05). Conclusion Butyrate has a significant antihypertensive effect on hypertensive rats, which may be related to the activation of GPR41/43 pathway to increase vasodilation and inhibit expression of inflammatory factors..

Key words: butyrates, hypertension, receptors, G-protein-coupled, interleukin-6, tumor necrosis factor-alpha, nitric oxide synthase type Ⅲ

中图分类号:

R349.6

图/表 6

参考文献 19

[1]	JIN M, QIAN Z, YIN J, et al. The role of intestinal microbiota in cardiovascular disease[J]. J Cell Mol Med, 2019, 23(4):2343-2350. doi:10.1111/jcmm.14195.
[2]	李翠茹, 彭买姣, 谭周进. 肠道菌群相关短链脂肪酸的研究进展[J]. 世界华人消化杂志, 2022, 30(13):562-570.
	LI C R, PENG M J, TAN Z J. Progress in research of intestinal microbiota related short chain fatty acids[J]. World Chinese Journal of Digestology, 2022, 30(13):562-570. doi:10.11569/wcjd.v30.i13.562.
[3]	WANG L, ZHU Q, LU A, et al. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system[J]. J Hypertens, 2017, 35(9):1899-1908. doi:10.1097/HJH.0000000000001378.
[4]	闫宇涵, 王占黎, 胡海, 等. 基于气相色谱-飞行时间质谱联用技术的肾性高血压大鼠模型粪便代谢组学分析[J]. 实用心脑肺血管病杂志, 2021, 29(7):92-96.
	YAN Y H, WANG Z L, HU H, et al. Fecal metabonomics in renal hypertensive rats based on gas chromatography-time-of-flight mass spectrometry technology[J]. Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease, 2021, 29(7):92-96. doi:10.12114/j.issn.1008-5971.2021.00.151.
[5]	ONYSZKIEWICZ M, GAWRYS-KOPCZYNSKA M, KONOPELSKI P, et al. Butyric acid,a gut bacteria metabolite,lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors[J]. Pflugers Archiv, 2019, 471(11/12)1441-1453. doi:10.1007/s00424-019-02322-y.
[6]	KIM S, GOEL R, KUMAR A, et al. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure[J]. Clin Sci(Lond), 2018, 132(6):701-718. doi:10.1042/CS20180087.
[7]	李景文, 龙村. 血管内皮的收缩和舒张因子研究进展[J]. 中国体外循环杂志, 2004, 2(1):61-63,48.
	LI J W, LONG C. Research progress on contractile and diastolic factors of vascular endothelium[J]. Chin J ECC, 2004, 2(1):61-63,48. doi:10.13498/j.cnki.chin.j.ecc.2004.01.026.
[8]	KUMAR G, DEY S K, KUNDU S. Functional implications of vascular endothelium in regulation of endothelial nitric oxide synthesis to control blood pressure and cardiac functions[J]. Life Sci, 2020, 259:118377. doi:10.1016/j.lfs.2020.118377.
[9]	JANIĆ M, LUNDER M, ZUPAN J, et al. The low-dose atorvastatin and valsartan combination effectively protects the arterial wall from atherogenic diet-induced impairment in the guinea pig[J]. Eur J Pharmacol, 2014, 743:31-36. doi:10.1016/j.ejphar.2014.09.027.
[10]	徐嘉欣, 殷立平. 炎症在高血压肾损害中的研究进展[J]. 中国处方药, 2022, 20(4):189-191.
	XU J X, YIN L P. Research progress of inflammation in hypertensive renal damage[J]. Journal of China Prescription Drug, 2022, 20(4):189-191.
[11]	傅为武, 李旷怡, 张英俭, 等. 高血压炎症反应与血压达标及动脉硬化相关性[J]. 中医学报, 2022, 37(6):1185-1191.
	FU W W, LI K Y, ZHANG Y J, et al. Research progress on relationship between hypertensive inflammatory response,blood pressure reaching standard and arteriosclerosis[J]. Acta Chinese Medicine, 2022, 37(6):1185-1191. doi:10.16368/j.issn.1674-8999.2022.06.218.
[12]	陈亮, 刘晓华, 宋明慧, 等. 高血压病患者血清白细胞介素-6的变化与临床意义[J]. 中国医药指南, 2016, 14(21):134-135.
	CHEN L, LIU X H, SONG M H, et al. Changes and clinical significance of serum interleukin-6 in patients with hypertension[J]. Guide of China Medicine, 2016, 14(21):134-135. doi:10.15912/j.cnki.gocm.2016.21.116.
[13]	王青梅, 冯玉宝, 李永玲, 等. 降压治疗对原发性高血压患者血压及血清IL-6、TNF-α季节性变异的影响[J]. 中华临床医师杂志(电子版), 2015, 9(23):4325-4330.
	WANG Q M, FENG Y B, LI Y L, et al. Impact of antihypertension on seasonal variability of blood pressure,serum IL-6,TNF-α levels in essential hypertension[J]. Chin J Clinicians(Electronic Edition), 2015, 9(23):4325-4330. doi:10.3877/cma.j.issn.1674-0785.2015.23.014.
[14]	SILVEIRA-NUNES G, DURSO D F, DE OLIVEIRA JR L R A, et al. Hypertension is associated with intestinal microbiota dysbiosis and inflammation in a Brazilian population[J]. Front Pharmacol, 2020, 11:258. doi:10.3389/fphar.2020.00258.
[15]	陈华青, 刘明耀. G蛋白偶联受体及其信号转导在免疫与炎症中的作用[J]. 现代免疫学, 2009, 29(6):441-446.
	CHEN H Q, LIU M Y. G protein-coupled receptors and their signal transduction in immunity and inflammation[J]. Current Immunology, 2009, 29(6):441-446.
[16]	魏钰倩, 苏文星, 季江, 等. G蛋白偶联受体在肥大细胞激活中的作用研究进展[J]. 中国皮肤性病学杂志, 2021, 35(5):565-569.
	WEI Y Q, SU W X, JI J, et al. Research progress on the role of G protein-coupled receptors in mast cell activation[J]. Chin J Derm Venereol, 2021, 35(5):565-569. doi:10.13735/j.cjdv.1001-7089.202007034.
[17]	杜红霞, 肖光旭, 杜晓鹂, 等. G蛋白偶联受体在血压调节中的新作用[J]. 中国中药杂志, 2021, 46(1):6-14.
	DU H X, XIAO G X, DU X L, et al. New effect of G-protein coupled receptors on blood pressure regulation[J]. China Journal of Chinese Materia Medica, 2021, 46(1):6-14. doi:10.19540/j.cnki.cjcmm.20200930.601.
[18]	张欢敏, 汪艳, 常广军, 等. 高精料对奶山羊盲肠中SCFAs-GPR41/43介导的炎症反应的影响[J]. 畜牧与兽医, 2018, 50(2):61-66.
	ZHANG H M, WANG Y, CHANG G J, et al. Effect of high-concentrate diet on the inflammatory response mediated by short-chain fatty acids-GPR41/43 in cecum of lactating goats[J]. Animal Husbandry ＆ Veterinary Medicine, 2018, 50(2):61-66.
[19]	NATARAJAN N, HORI D, FLAVAHAN S, et al. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41[J]. Physiol Genomics, 2016, 48(11):826-834. doi:10.1152/physiolgenomics.00089.2016.

组别	造模前	造模4周	给药2周	给药4周
假手术组	100.3±7.2	100.2±4.8	99.9±5.9	101.5±6.4
对照组	99.7±6.8	154.9±8.2^a	152.7±5.9^a	153.4±5.4^a
缬沙坦组	100.6±7.8	156.8±9.2^a	143.0±10.2^ab	133.1±6.1^ab
丁酸低剂量组	101.6±5.6	159.5±10.6^a	144.5±9.2^ab	139.6±5.8^abc
丁酸高剂量组	100.4±5.5	159.4±8.9^a	138.7±6.3^abd	131.2±5.3^abd
F	0.181	129.073^＊＊	107.884^＊＊	160.446^＊＊

组别	造模前	造模4周	给药2周	给药4周
假手术组	100.3±7.2	100.2±4.8	99.9±5.9	101.5±6.4
对照组	99.7±6.8	154.9±8.2^a	152.7±5.9^a	153.4±5.4^a
缬沙坦组	100.6±7.8	156.8±9.2^a	143.0±10.2^ab	133.1±6.1^ab
丁酸低剂量组	101.6±5.6	159.5±10.6^a	144.5±9.2^ab	139.6±5.8^abc
丁酸高剂量组	100.4±5.5	159.4±8.9^a	138.7±6.3^abd	131.2±5.3^abd
F	0.181	129.073^＊＊	107.884^＊＊	160.446^＊＊

组别	造模前	造模4周	给药2周	给药4周
假手术组	337±41	347±65	348±72	349±35
对照组	344±63	372±46	373±36	381±27
缬沙坦组	336±48	373±39	368±53	358±61
丁酸低剂量组	349±37	373±37	367±57	364±43
丁酸高剂量组	341±45	374±42	362±60	358±47
F	0.214	0.873	0.457	1.167

组别	造模前	造模4周	给药2周	给药4周
假手术组	337±41	347±65	348±72	349±35
对照组	344±63	372±46	373±36	381±27
缬沙坦组	336±48	373±39	368±53	358±61
丁酸低剂量组	349±37	373±37	367±57	364±43
丁酸高剂量组	341±45	374±42	362±60	358±47
F	0.214	0.873	0.457	1.167

组别	eNOS	IL-6	TNF-α
假手术组	112.44±3.07	157.59±7.45	275.85±13.49
对照组	69.90±4.16^a	279.77±5.12^a	481.33±11.57^a
缬沙坦组	87.23±5.86^ab	238.73±10.25^ab	401.23±26.68^ab
丁酸低剂量组	79.87±5.60^abc	246.68±13.53^ab	456.36±24.84^abc
丁酸高剂量组	80.44±6.79^ab	230.55±14.13^abd	371.28±25.57^abcd
F	138.930^＊＊	256.736^＊＊	213.185^＊＊

丁酸通过激活G蛋白偶联受体41/43通路降低高血压大鼠血压

Butyrate reduces blood pressure in hypertensive rats by activating the G protein-coupled receptor 41/43 pathway

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 6

参考文献 19

相关文章 15

编辑推荐

Metrics

本文评价

组别	eNOS	IL-6	TNF-α
假手术组	1.00±0.03	1.00±0.02	1.00±0.02
对照组	0.46±0.01^a	1.83±0.11^a	2.20±0.01^a
缬沙坦组	0.72±0.05^ab	1.34±0.10^ab	1.38±0.04^ab
低剂量丁酸组	0.58±0.04^abc	1.44±0.10^ab	1.49±0.03^abc
高剂量丁酸组	0.64±0.07^ab	1.31±0.06^abd	1.32±0.02^abcd
F	108.570^＊＊	61.801^＊＊	1 310.029^＊＊

组别	GPR41	GPR43
假手术组	0.26±0.02	0.30±0.01
对照组	0.27±0.02	0.31±0.01
缬沙坦组	0.29±0.02^ab	0.32±0.02
丁酸低剂量组	0.36±0.02^abc	0.38±0.02^abc
丁酸高剂量组	0.38±0.02^abc	0.40±0.02^abcd
F	64.153^＊＊	39.884^＊＊

[1]	高攀, 谢冰歆, 周赞东, 刘彤. 慢性肾脏病循环中FGF23对心房纤维化的促进作用[J]. 天津医药, 2024, 52(9): 917-923.
[2]	范慧慧, 任玉梅, 田新磊, 张凯, 李晓丽. 止咳平喘方对支气管哮喘小鼠气道炎症及TLR4/TRAF6/NF-κB通路的影响[J]. 天津医药, 2024, 52(9): 924-929.
[3]	贾维宁, 鲍亚玲, 雷慧, 殷晓宁. 夏枯草提取物对脓毒症小鼠炎症反应和腹腔巨噬细胞的影响[J]. 天津医药, 2024, 52(9): 930-935.
[4]	焦爱菊, 任宝龙, 张春花, 李文瑞, 赵玮婧. NIHSS评分联合血清BDNF、IL-6对脑卒中后抑郁的预测价值[J]. 天津医药, 2024, 52(9): 963-966.
[5]	徐琼芳, 钟斐, 李子帅. 淫羊藿苷调节SDF-1/CXCR4信号通路对多囊卵巢综合征大鼠卵巢颗粒细胞凋亡的影响[J]. 天津医药, 2024, 52(7): 727-732.
[6]	李勇, 苏亚坤, 张宏博, 李原, 李占虎, 闫小菊. 原发性高血压早期肾损害患者血清白脂素水平的临床意义[J]. 天津医药, 2024, 52(6): 609-613.
[7]	赵术彤, 丁运, 李月川, 赵晓赟, 耿华, 徐美林. 轻度慢性阻塞性肺疾病的病理特征及其与炎性因子的相关性[J]. 天津医药, 2024, 52(6): 643-647.
[8]	叶朝阳, 马建中, 李后俊, 魏鲲鹏. 急性胰腺炎患者外周血TLR4、IL-1β、NLR水平与疾病进展和预后的关系[J]. 天津医药, 2024, 52(6): 648-652.
[9]	陈惠刚, 池小锋, 封娣, 米娅莉. 黄芪甲苷抑制Fas/FasL信号通路减轻创伤性脑损伤大鼠神经功能缺损和神经元凋亡[J]. 天津医药, 2024, 52(5): 469-474.
[10]	张兴光, 王邦茂, 刘涛涛, 张文成, 董艳美, 李小青, 牛海艳, 夏时海. 高原IBS与肠屏障损伤、炎性介质及神经递质的相关性研究[J]. 天津医药, 2024, 52(5): 499-504.
[11]	郑康鹏, 唐鑫国, 徐琦, 樊钰亭, 梁博, 付晓伟, 方路. 胆囊癌根治手术成功实施列线图预测模型的建立和验证[J]. 天津医药, 2024, 52(5): 536-540.
[12]	田静, 王子龙, 肖丹娜, 范向飞. 不同咀嚼压力对大鼠正畸移动牙压力侧牙槽骨改建的影响[J]. 天津医药, 2024, 52(4): 367-371.
[13]	田佳玉, 冯丹, 胡焓, 张书力, 童胜雄, 李少军. 槲皮素通过抑制MIP-1α/CCR1/CCR5信号通路减轻大鼠带状疱疹后神经痛的机制[J]. 天津医药, 2024, 52(3): 256-260.
[14]	张文超, 杨雪辉, 尹涛, 王睿健, 张盟盟. 自发性急性脑出血患者血浆sCD163/sTWEAK比值与预后的关系[J]. 天津医药, 2024, 52(3): 297-301.
[15]	张丽冉, 赵延华. MP妊高征监测系统联合PLGF和PI对子痫前期的预测价值[J]. 天津医药, 2024, 52(3): 306-310.