大鼠非酒精性单纯性脂肪肝中肾素血管紧张素系统两条通路的相互作用研究

doi:10.11843/j.issn.0366-6964.2019.11.015

Abstract

Abstract: This experiment explored the mutual antagonism of ACE/AngⅡ/AT1R and ACE2/Ang1-7/MasR pathways in the renin angiotensin system (RAS) in rats nonalcoholic simple fatty liver (NAFL). Thirty male Sprague-Dawley rats were randomly divided into normal control group, model group and medication group. In addition to the normal control group, the other two groups were fed with high-fat diet, and each rat of medication group was given 50 mg·(kg·d)^-1 vitastatin. Blood was collected and all rats were killed after 6 weeks,liver samples were taken at the same time. The contents of TG, ALT and AST in serum of each group were determined. The activities of·OH, TNOS, SOD and T-AOC in liver tissue were determined. The release of AngⅡ, Ang1-7 and inflammatory factors in tissue homogenate were determined by ELISA. The levels of ACE, ACE2, AT1R and MasR in liver tissue were analyzed by Western blotting. HE staining was conducted to observe liver pathological changes. Results were as follows:In the model group,the liver index was significantly increased (P<0.05); Serum TG, AST and ALT levels were significantly increased (P<0.01); Liver pathology showed changes in steatosis; Oxidative stress and release of inflammatory factors in liver tissue increased significantly. The expression of ACE, AT1R protein and the amount of AngⅡ and Ang1-7 increased significantly (P<0.05); The protein expression of ACE2 and MasR decreased significantly (P<0.05), and the ratio of ACE/ACE2 increased (P<0.01). The medication group improved the damage of oxidative stress and inflammation, and improved liver damage by down-regulating the ACE/AngⅡ/AT1R pathway. High-fat feeding for 6 weeks can induce simple fatty liver in rats, and both the two pathways in the local RAS system are activated. Abnormal activation of the ACE/AngⅡ/AT1 pathway leads to oxidative stress and inflammatory response in the liver, while the ACE2/Ang1-7/MasR pathway has the opposite effect. It is suggested that endogenous ACE2 produced by the liver may play an important role in the prevention of NAFL by mediating the activation of the Ang1-7/MasR pathway in exogenous stimuli-induced liver injury.

CLC Number:

S852.23

LIU Ying, WANG Huanhuan, YAN Shuping, ZHU Bin, ZHANG Yuanshu. Study on the Interaction of Two Pathways of Renin Angiotensin System in Rat Nonalcoholic Simple Fatty Liver[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(11): 2309-2317.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://www.xmsyxb.com/EN/10.11843/j.issn.0366-6964.2019.11.015

https://www.xmsyxb.com/EN/Y2019/V50/I11/2309

References 21

[1]	STANKOVIC M N, MLADENOVIC D R, DURICIC I, et al. Time-dependent changes and association between liver free fatty acids, serum lipid profile and histological features in mice model of nonalcoholic fatty liver disease[J]. Arch Med Res, 2014, 45(2):116-124.
[2]	WILLIAMSON R M, PRICE J F, GLANCY S, et al. Prevalence of and risk factors for hepatic steatosis and nonalcoholic fatty liver disease in people with type 2 diabetes:the edinburgh type 2 diabetes study[J]. Diabetes Care, 2011, 34(5):1139-1144.
[3]	PATEL V B, CLARKE N, WANG Z C, et al. Angiotensin Ⅱ induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17:a positive feedback mechanism in the RAS[J]. J Mol Cell Cardiol, 2014, 66:167-176.
[4]	SANTOS R A S, SAMPAIO W O, ALZAMORA A C, et al. The ace2/angiotensin-(1-7)/Mas axis of the renin-angiotensin system:focus on angiotensin-(1-7)[J]. Physiol Rev, 2018, 98(1):505-553.
[5]	DE MACÊDO S M, GUIMARÃES T A, FELTENBERGER J D, et al. The role of renin-angiotensin system modulation on treatment and prevention of liver diseases[J]. Peptides, 2014, 62:189-196.
[6]	SIMÕES E SILVA A C, SILVEIRA K D, FERREIRA A J, et al. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis[J]. Br J Pharmacol, 2013, 169(3):477-492.
[7]	VERGNIOL J, BARBU V, LEMOINE M, et al. 873 progression of NAFLD in humans is associated with the activation of the renin-angiotensin system[J]. J Hepatol, 2011, 54(S1):S348.
[8]	汪亮. 肾素-血管紧张素系统在非酒精性脂肪肝发病中的作用[J]. 重庆医学, 2010, 39(22):3139-3141, 3149.
	WANG L. The role of renin-angiotensin system in the pathogenesis of nonalcoholic fatty liver disease[J]. Chongqing Medicine, 2010, 39(22):3139-3141, 3149. (in Chinese)
[9]	LIU B, WU R, ZHANG W, et al. Fosinopril improves liver fibrosis by upregulating ACE2/Angiotensin-(1-7) axis activation in rats with nonalcoholic steatohepatitis[J]. Lat Am J Pharm, 2012, 31(4):588-596.
[10]	CAO X, YANG F Y, SHI T T, et al. Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis activates Akt signaling to ameliorate hepatic steatosis[J]. Sci Rep, 2016, 6:21592.
[11]	CENGIZ M, OZENIRLER S, YILMAZ G, et al. Impact of hepatic immunoreactivity of angiotensin-converting enzyme 2 on liver fibrosis due to non-alcoholic steatohepatitis[J]. Clin Res Hepatol Gastroenterol, 2015, 39(6):692-698.
[12]	WANG K, LIU X Q, XIAO H, et al. The correlation between inflammatory injury induced by LPS and RAS in EpH4-Ev cells[J]. Int Immunopharmacol, 2017, 46:23-30.
[13]	中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018更新版)[J]. 传染病信息, 2018, 31(5):393-402, 420.
	Fatty Liver and Alcoholic Liver Disease Group, Society of Hepatology, Chinese Medical Association, Chinese Medical Association Fatty Liver Disease Expert Committee. Guidelines of prevention and treatment for nonalcoholic fatty liver disease:a 2018 update[J]. Infectious Disease Information, 2018, 31(5):393-402, 420. (in Chinese)
[14]	DAY C P, JAMES O F W. Steatohepatitis:a tale of two "hits"?[J]. Gastroenterology, 1998, 114(4):842-845.
[15]	SANTOS R A S, SIMOES E SILVA A C, MARIC C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas[J]. Proc Natl Acad Sci U S A, 2003, 100(14):8258-8263.
[16]	YAN Z G, FAN R F, YIN S J, et al. Protective effects of Ginkgo biloba leaf polysaccharide on nonalcoholic fatty liver disease and its mechanisms[J]. Int J Biol Macromol, 2015, 80:573-580.
[17]	WU Y, MA K L, ZHANG Y, et al. Lipid disorder and intrahepatic renin-angiotensin system activation synergistically contribute to non-alcoholic fatty liver disease[J]. Liver Int, 2016, 36(10):1525-1534.
[18]	SANTOS S H S, ANDRADE J M O, FERNANDES L R, et al. Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet[J]. Peptides, 2013, 46:47-52.
[19]	CAO X, SONG L N, ZHANG Y C, et al. Angiotensin-converting enzyme 2 inhibits endoplasmic reticulum stress-associated pathway to preserve nonalcoholic fatty liver disease[J]. Diabetes Metab Res Rev, 2019, 35(4):e3123.
[20]	霍苗苗, 程变巧,林伟国,等. 扶正化瘀方对非酒精性脂肪性肝病大鼠肝纤维化及ACE-Ang Ⅱ-AT1R轴的影响[J]. 解放军医学杂志, 2018, 43(2):114-119.
	HUO M M, CHENG B Q, LIN W G, et al. Therapeutic effects of Fuzhenghuayu decoction on nonalcoholic steatohepatic fibrosis rats by regulating ACE-AngⅡ-AT1R axis[J]. Medical Journal of Chinese People's Liberation Army, 2018, 43(2):114-119. (in Chinese)
[21]	刘颖,王凯,纪晓霞,等. 肾素血管紧张素系统(RAS)两条轴相互负向调节与大鼠非酒精性脂肪肝病(NAFLD)肝损伤的关系研究[J]. 畜牧与兽医, 2019, 51(5):48-54.
	LIU Y, WANG K, JI X X, et al. Relationship between negative reversal of two axes of renin angiotensin (RAS) and liver injury induced by non-alcoholic fatty liver disease (NAFLD) in rats[J]. Animal Husbandry & Veterinary Medicine, 2019, 51(5):48-54. (in Chinese)

Study on the Interaction of Two Pathways of Renin Angiotensin System in Rat Nonalcoholic Simple Fatty Liver

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 21

Related Articles 13

Recommended Articles

Metrics

Comments

[1]	JIN Meilin, LI Taotao, SUN Dongxiao, WEI Caihong. Research Progress of Epigenetic Regulation in Fat Deposition Mechanism of Livestock and Poultry [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 855-867.
[2]	CHEN Miaomiao, TONG Xishuai, ZHENG Jiaming, ZHAO Hongyan, GU Jianhong, LIU Zongping. Effects of 5-amino-imidazole-4-carboxamide Nucleotide on Autophagy and Differentiation in Osteoclasts [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(11): 2339-2347.
[3]	LI Zhiqiang, YAN Shuping, JI Xiaoxia, WANG Kai, ZHANG Yuanshu. Distribution and Expression of Angiotensin-Converting Enzyme 2 (ACE2) in the Jejunum of Piglets and Its Relationship with Substance Transport [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(8): 1676-1684.
[4]	WEI Yu-shuang, LIU Jiao-yang, HAN Ying-qian, GUO Zhen-zhen, LIU Xiao-he, BA Gen, HAN Li-qiang, WANG Jiang, CHU Bei-bei, YANG Guo-yu. Construction of shRNA Library of Chlorocebus Sabaeus Cathepsin Genes and the Establishment of Its Stable Transfection Cell Lines [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(6): 1282-1290.
[5]	LI Long-long, PENG Meng-ling, WANG Dian, YU Lei, GE Chong-yang, MA Hai-tian. The Effect of (一)-Hydroxycitric Acid on Proliferation and Mitochondria Function in Cultured Primary Chicken Hepatocytes [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(5): 945-953.
[6]	NIE Pei-ting，TANG Cheng，YUE Hua. Activation of Cold-inducible RNA-binding Protein by H1N1 Influenza Virus Contributes to Viral Replication Via Activating NF-κB Pathway [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2016, 47(10): 2108-2114.
[7]	NIE Pei-ting，TANG Cheng，YUE Hua. Cold-inducible RNA Binding Protein of Mice Involved in Response to Influenza A Virus Infection in Mice [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2016, 47(8): 1652-1657.
[8]	QUAN Su-yu，ZHANG Yuan-shu，BU Deng-pan . Heat Stress-induced Cell Injury and Effects on the Gene Expression of Milk Synthesis-related Transporters in Dairy Cow [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2016, 47(8): 1704-1713.
[9]	CHAI Ji-tian，JIANG Jun-na，LI Dong，WANG Jian-bing，ZHOU Jia-hua，LI Ying-ying，WANG Zhi-qiang. Analysis of CRE and SRE Response Element in the Porcine CCR1 and CCR5 Signal Pathway [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(9): 1650-1655.
[10]	GUO Bao-ping，XU Ming-long，HU Jin，XU Yin-xue. Studies on Changes of Sexual Organs and Their Related Hormones during the Early Phase in Dehydroepiandrosterone-induced Female Rat Polycystic Ovarian Syndrome Model [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(8): 1348-1355.
[11]	PAN Hong-bin，ZHAO Su-mei，SUN Ze-wei，LONG Guo-hui，GAO Shi-zheng，QIN Gui-xin. Fat-specific Protein 27 (Fsp27) and Lipid Metabolism [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2014, 45(3): 347-353.
[12]	YANG Fan, TANG Cheng, YUE Hua. Interference of Chicken Heat Shock Protein 70 Gene Expression Induced ChickenEmbryo Fibroblast Apoptosis [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2013, 44(3): 459-464.
[13]	HAN Haozhe, TIE Zihang, PANG Weijun, CAI Rui. Advances of IGF2BP2-Mediated m⁶A Modification on Animal Fat Deposition [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(9): 3605-3612.