| Background and objective:Liver fibrosis,a large amount of extracellular matrix deposition,which is the intermediate process of varieties chronic liver disease to cirrhosis.There are many complications and poorer prognosis in liver fibrosis.However,the treatment of liver fibrosis is not very clear and these are seriously affect the patient’s quality of life.So we urgently need to explore new treatments and drugs to treat liver fibrosis.Renin angiontensin aldosterone system(RAAS)are included in angiotensinconverting enzyme(ACE),Angiotensin Ⅱ(AngⅡ),angiotensin Ⅱ type 1 repector(AT1R),angiot ensin-converting enzyme2(ACE2),angiotensin-(1-7)(Ang-(1-7)),then many research ers had verified the important role of the component of renin angiontensin aldostero ne system in the progression of liver fibrosis.Hence,we speculated RAAS May be one of new ideal targets in the intervention of liver fibrosis.Lipoxins(LXs)are biologically active productions of arachidonic acid,posse ssed pro-resolving,anti-inflammatory,antioxidation,antitumor,proliferation and apoptosis properties.The precursor and receptors of Lipoxin(LXs)are abundant in normal liver tissues,so its protective effect on the liver disease is more and more attention.This subject mainly discussed the mechanism of Lipoxin on liver fibrosis through regulating the component of RAAS.Methods:1.Detect Copy of liver fibrosis.Forty Sprague–Dawley male rats,abou180-220 g,grandomly divided into four groups,each group of ten as following:(1)Normal control group:subcutaneous injection of olive oil in rats 1.8 ml/kg.(2)Model group:3 mL/kg body weight of 40 % CCL4/olive oil(4:6,v/v)by hypoderm-ic injection twice weekly for up to10 weeks.(3)BML-111 group: received BML-111(1mg/kg)twice weekly by hypodermic injecti-on 30 min prior to inject 40 % CCL4/olive oil as model group.(4)BOC-2 groupwere injected with CCL4,and received BOC-2(50 m g/kg)twice week-ly by hypodermic injection 30 min prior to inject BML-111 as BML-111 group.2.Confirmed the anti liver fibrosis of LXSs.(1)Hematoxylin eosin staining : observed liver tissus structure change of microscopic.(2)Masoon staining:observed liver tissue collagen deposition of microscopic.(3)The activities of aspartate aminotransferase(AST)and alanine aminotrans-ferase(ALT)in serum were assessed: evaluated liver function damage degree.(4)Hydroxyproline Content was assessed: to measure the degree of liver fibrosis.3.Explore the mechanism anti liver fibrosis of LXSs.(1)The activities of ACE and ACE2 in liver tissue were assessed.(2)The content of Ang Ⅱ,ACE,Ang(1-7),CE2 in serum and liver tissue were assessd by ELISA.(3)The mRNA expression level ofAng Ⅱ,Ang1-7,AT1 R,Mas were assessd by qPCR.(4)The content of Ang Ⅱ,AT1 R,Ang(1-7),Mas in liver tissue were assessd by Wes-tern Blot.Result:1.BML-111 alleviated CCL44-induced hepatic injury,inhibited inflammation.2.BML-111 alleviated collagen deposition in LiverTissue of CCL4 treated rats.3.BML-111 inhibited the activities of AST and ALT in serum.4.BML-111 reduced the content of ACE in serum and liver tissue of CCL4 treated rats.5.BML-111 inhibited the activities of ACE in liver tissue..6.BML-111 alleviated the content of Ang Ⅱ in serum and liver tissue of CCL4 treated rats.7.BML-111 inhibited the mRNA and protein expression level of Ang Ⅱ and AT1 R of CCL4 treated rats.8.BML-111 increased the content of ACE2 and activities of ACE2 in livertissue.9.BML-111 increased the content of Ang-(1-7)in liver tissue of CCL4 treated rats.10.BML-111 up-regulated the mRNA and protein expression level of Ang-(1-7)and Mas of CCL4 treated rats.Conclusion:BML-111 have an anti-fibrosis effects,which may be relation with the balance of ACE-AngⅡ-AT1 R axis and ACE2-Ang-(1-7)-Mas axis. |
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