Li Yao^*, Yun-Long Zhang, Jue Li, Jing Yu, Yan Peng

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Pharmacy College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China..
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Abstract: Objective: To study the effect of Biejiajian Oral Liquid (BOL) on the rennin angiotensin aldosterone system (RAAS) in plasma of hepatic fibrosis rats and in hepatic stellate cell (HSC) of normal rats. We explore the mechanism of BOL on inhibiting the activation of HSC and illustrate its mechanism of anti-hepatic fibrosis further. Methods: SD Rats were divided into 5 groups randomly: normal control group, model group, Enalapril group and BOL groups with different concentration (2.0 g/ml or 1.0 g/ml). Every group was administered with CCl4 and olive oil solution to induce hepatic fibrosis except normal one. Each group was treated with the respective drug for 5 weeks and then got the blood. The level of renin, angiotensin II and aldosterone in the plasma of liver fibrosis rats were detected by the radioimmunoassay. By using reverse transcription-polymerase chain reaction (RT-PCR) to measure the gene expression of the rennin, ACE, angiotensinogen, AT1R and ALD. The AT1R gene expression in normal HSC was determined by the immunohistochemical measurement. Results: BOL could effectively reduce the activity of the PRA, AngIIand ALD, which showed a significant effect on the inhibition of the AngII (P < 0.01). Meanwhile, compared with the normal control group, there was a notable inhibitory action on the PRA of HSC which was administrated by serum containing BOL (P < 0.05). And yet, drug applied group showed no difference with the model group for other factors of the RAAS. Conclusion: BOL can inhibit the expression of RAAS in the rat plasma and can inhibit the expression of the mRNA of renin in the normal HSC, which could be the mechanism of anti-hepatic fibrosis.

Keywords: Hepatic Fibrosis; RAAS; Biejiajian Oral Liquid; Serum Pharmacology; Rat

Cite this paper: L. Yao, Y. Zhang, J. Li, J. Yu and Y. Peng, "Effect of Biejiajian Oral Liquid on the Expression of RAAS in Hepatic Fibrosis Rats," Pharmacology & Pharmacy, Vol. 3 No. 3, 2012, pp. 322-327. doi: 10.4236/pp.2012.33043.

References

[1]   Lamireau T, Desmouliere A, Bioulac-Sage P, et al., “Mechanisms of hepatic fibrogenesis,” Arch Pediatr, Vol. 9, No. 4, 2002, pp. 392-405.

[2]   Kanzler S, Lohse AW, Keil A, et al., “TGF-beta 1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis,” Am J Physiol, Vol. 276, No. 4, 1999, pp. 1059-1068.

[3]   Paizis G, Gilbert RE, Cooper ME, et al., “Effects of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis,” J Hepatol, Vol.35, 2001, pp. 376-385.

[4]   Yoshi ji H, Yoshii J, Ikenaka Y, et al., “Inhibition of renin-angiotensin system attenuates liver enzyme-altered preneoplastic lesions and fibrosis development in rats,” Journal of Hepatology, Vol. 37, 2002, pp. 22-30.

[5]   Albanis E, Friedman SL, “Hepatic fibrosis.Pathogenesis and principles of Therapy,” Clinics in Liver disease, Vol. 5, No. 2, 2001, pp. 315-334.

[6]   Lamireau T, Desmouliere Bioulac-Sage P, et a1., “Mechanisms of hepatic Fibrogenesis,” ArchPediatr, Vol. 9, No. 4, 2002, pp. 392-405.

[7]   Friedman SL, “Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury,” J Biol Chem, Vol. 275, 2000, pp. 2247-2250.

[8]   Jonsson JR, Clouston AD, Ando Y, et al., “Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis,” Gastroenterology, Vol. 121, 2001, pp. 148-155.

[9]   Wei HS, Li DG, Lu HM, et al., “Effects of AT1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl4,” World J Gastroentero, Vol. 6, No. 4, 2000, pp. 540-545.

[10]   Bataller R, Gines P, Nicolas JM, et a1., “Angiotensin II induces contraction and proliferation of human hepatic stellate cells,” Gastroenterology, Vol. 118, No. 6, 2000.

[11]   Li Yao, Zhen-Min Yao, Yu Tao, “Therapeutic research of Biejia Jian oral liquid in hepatofibrotic rats,” Pharmacology and Clinics of Chinese Materia Medica, Vol. 18, 2002, pp. 6-5.

[12]   Li Yao, Zhen-Min Yao, Yu Tao, “Influence of BOL on hyaluronic acid, laminin and hyperplasia in hepato-fibrotic rats,” World J Gastroenterol, 2001; Vol. 7, No. 6, pp. 872-875.

[13]   Diana N, D’Ambrosio, José L. Walewski, Robin D. Clugston, et al., “Distinct Populations of Hepatic Stellate Cells in the Mouse Liver Have Different Capacities for Retinoid and Lipid Storage,” P LoS One, Vol. 6, No. 9, 2011, pp. e24993.

[14]   Carlos M, Ferrario MD, “Addressing the theoretical and clinical advantages of combination therapy with inhibitors of the renin-angiotensin-aldosterone system: antihypertensive effects and benefits beyond BP control,” Life Sci, Vol. 86, No. (9-10), 27 February 2010, pp. 289–299.

[15]   Christian W, Mende, “Application of Direct Renin Inhibition to Chronic Kidney Disease,” Cardiovasc Drugs Ther, Vol. 24, No. 2, April 2010, pp. 139–149.

[16]   Terry KW Ma, Kevin KH Kam, Bryan P Yan, et al., “Renin–angiotensin–aldosterone system blockade for cardiovascular diseases: current status,” Br J Pharmacol, Vol. 160, No. 6, July 2010, pp. 1273–1292.

[17]   Andrew Leask, Shaoqiong Chen, Daphne Pala, et al., “Regulation of CCN2 mRNA expression and promoter activity in activated hepatic stellate cells,” J Cell Commun Signal, Vol. 2, No. (1-2), June 2008, pp. 49–56.

[18]   Marike Marjolijn van Beuge, Jai Prakash, Marie Lacombe, et al., “Increased Liver Uptake and Reduced Hepatic Stellate Cell Activation with a Cell-Specific Conjugate of the Rho-kinase Inhibitor Y27632,” Pharm Res, Vol. 28, No. 8, August 2011, pp. 2045–2054.

[19]   Raghow R, “The role of extracellular matrix in postinflammatory wound healing and fibrosis,” Faseb J, Vol. 8, 1994, pp. 823–31.

[20]   Zhao-Yang Ye, Houssein HSH, Mahato RI, “Bioconjugation of oligonuc-leotides for treating liver fibrosis,” Oligonucleotides, Vol. 17, No. 4, 2007 Winter, pp. 349-404.

[21]   Feng-Rui Yang, Bu-Wu Fang, Jian-Shi Lou, “Effects of Haobie Yangyin Ruanjian Decoction on hepatic fibrosis induced by carbon tetrachloride in rats,” World J Gastroenterol, Vol. 16, No. 12, 28 March 2010, pp. 1458-1464.

[22]   Yun-Xiao Zhou, Jiu Chen, Jian-Ping Li, Yan-Li Wang, Xiao-Dong Jin, “Chinese Medicinal Herbs in Treating Model Rats with Hepatic Fibrosis,” Afr J Tradit Complement Altern Med, Vol. 7, No. 2, 2010, pp. 104–108.

[23]   Martina Buck, Mario Chojkier, “A Ribosomal S-6 Kinase–Mediated Signal to C/EBP-β Is Critical for the Development of Liver Fibrosis,” P LoS ONE, Vol. 2, No. 12, 2007, pp. e1372.

[24]   Erica Novo, Maurizio Parola, “Redox mechanisms in hepatic chronic wound healing and fibrogenesis,” Fibrogenesis Tissue Repair, Vol. 1, 2008, pp. 5.

[25]   Annika Sommerfeld, Roland Reinehr, Dieter H?ussinger, “Bile Acid-induced Epidermal Growth Factor Receptor Activation in Quiescent Rat Hepatic Stellate Cells Can Trigger Both Proliferation and Apoptosis,” J Biol Chem, Vol. 284, No. 33, 14 August 2009, pp. 22173–22183.

[26]   Shu X, McCulloch M, Gao J, et al., “Chinese herbal medicine and chemotherapy in the treatment of hepatocellular carcinoma: a meta-analysis of randomized controlled trials,” Integrative Cancer Therapies, Vol. 4, No. 3, 2005, pp. 219–229.

[27]   John S, Lubel, Chandana B, HERATH, Jorge tchongu, et al., “Angiotensin(1–7), an alternative metabolite of the renin–angiotensin system, is up-regulated in human liver disease and has anti?brotic activity in the bile-duct-ligated rat,” Clinical Science, Vol. 117, 2009, pp. 375–386.

[28]   Regina Maria Pereira, Robson Augusto Souza dos Santos, Filipi Leles da Costa Dias, et al., “Renin-angiotensin system in the pathogenesis of liver fibrosis,” World J Ga-stroenterol, Vol. 15, No. 21, 7 June 2009, pp. 2579-2586.

[29]   Gakuhei Son, Ian N. Hines, Jeff Lindquist, et al., “Inhibition of Phosphatidylinositol 3-Kinase Signaling in Hepatic Stellate Cells Blocks the Progression of Hepatic Fibrosis,” J Hepatology, Vol. 50, No. 5, November 2009, pp. 1512-1523.

[30]   Nishikawa Y, Ohi N, Yagisawa A, et al., “Suppressive effect of orthovanadate on Hepatic Stellate Cell Activation and Liver Fibrosis in Rats,” The American Journal of Pathology, No. 3, 2009.

[31]   Joanna M, Abrams, John W, Osborn, “A Role for Benzamil-Sensitive Proteins of the Central Nervous System in the Pathogenesis of Salt-Dependent Hypertension,” Clin Exp Pharmacol Physiol, Vol. 35, No. (5-6), May 2008, pp. 687–694.

[32]   Adam Whaley-Connell, Megan S Johnson, James R Sowers, “Aldosterone: Role in the Cardiometabolic Syndrome and Resistant Hypertension,” Prog Cardiovasc Dis, Vol. 52, No. 5, Mar–Apr 2010, pp. 401–409.

[33]   Raimund H, Pichler, Ian H, de Boer, “Dual Renin-Angiotensin-Aldosterone System Blockade for Diabetic Kidney Disease,” Curr Diab Rep, Vol. 10, No. 4, August 2010, pp. 297-305.

[34]   Wen-Li Wang, Carolyn A. Haller, Jing Wen, et al., “Decoupled Syndecan-1 mRNA and protein expression is differentially regulated by Angiotensin II in Macrophages,” J Cell Physiol, Vol. 214, No. 3, March 2008, pp. 750–756.

[35]   Sasaki k et al., Nature, Vol. 351, 1991, pp. 230,.

[36]   Henriksen JH, Kiszka-Kanowitz M, Bendtsen F, “Review article: volume expansion in patients with cirrhosis,” J Aliment Pharmacol Ther, Vol. 16, No. 5, 2002, pp. 12-23.

[37]   Duvoux C, Zanditenas D, Hezode C, et al., “Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: a pilot study,” J Hepatology, Vol. 36, No. 2, 2002, pp. 374-380.

[38]   Paizis G, Cooper ME, Schembri JM, et al., “Up-regulation of components of the renin-angiotensin system in the bile duet-ligated rat liver,” Gastroenterology, Vol. 123, No. 5, 2002, pp. 1667-1676.

[39]   Mifune M, Sasaxnura H, Shimizu H, et al., “AngiotensinIItype 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells,” Hypertension, Vol. 36, No. 5, 2000, pp. 845-850.

[40]   Lim D, Lutueuta S, Bachireddy P, et al., “Angiotensin II bloekade reverses myoeardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy,” J Circulation, Vol. 103, No. 6, 2001, pp. 789-91.

[41]   Yoshi ji H, Yoshii J, Ikenaka Y, et al., “Inhibition of renin-angiotensin system attenuates liver enzyme-altered preneoplastic lesions and fibrosis development in rats,” J Hepatology, Vol. 37, No. 1, 2002, pp. 22-30.

[42]   Xi-Shan Y, Xu L, Ping-Sheng W, et al., “CYP II β2 expression in rat liver and the effect of spironolactone on hepatic fibrogenesis,” J Hormone Research, Vol. 33, No. 6, 2000, pp. 288-93.