| Background Liver fibrosis is a disease which badly threatenpeople's health, there has no effective theraphy exists at present. A greatdeal of research have been performed to understand the cellar andmolecular mechanisms responsible for the development of liver fibrosis.The most characteristic feature of liver fibrosis is excess deposition ofextra-cellularmatrix proteins(ECM), which is a characteristic of mosttypes of chronic liver diseases. It is a forerunner to cirrhosis. Activatedhepatic stellate cell(HSC) is the primary cell type responsible for theexcess production of collagen and play a key role in hepatic fibrogenesis.It has been proved that TGF-βis a strong pro-fibrogenic cytokine. TGF-βand its downstream signaling CTGF plays an essential role in the processof hepatic fibrosis.Clinic observations indicate that chronic hepatitis B and C appear toprogress more rapidly in males than in females, and cirrhosis is lagerly adisease of man and postmenopausal women, the male:female ratio hasbeen reported to range from 2.3:1 to 2.6:1. Therefore sex hormone mayplay an important role in the progression from fibrosis to cirrhosis. Manyscholars have proved that estradiol has protective effect on liver fibrosisin the animal model and cell model. But the endogenous estradiol has itsshortcoming, it distributes in the whole body and causes many side-effects and was restricted it's clinical application. Thereforeenhancing target organs and target cells drug concentration, maximizingefficacy and minimizing adverse drug reaction appear very important.Theβ-estradiol nanoparticle we have made which have liver target maysolve this problem.Objective We first observed whetherβ-estradiol nanoparticle stillhad the same suppressive effect on HSCs proliferation and activation asβ-estradiol, and their effect on the expression of mRNA and protein ofTGF-β1 and its downstream signaling CTGF, then the difference wascompared between them. The anti- fibrotic mechanism ofβ-estradiol andβ-estradiol nanoparticles was further investigated, which provides us withmore theories basis to treat liver fibrosis.Methods (1) Hepatic stellate cells were treated with differentconcentration ofβ-estradiol andβ-estradiol nanoparticle, then their effecton the proliferation was detected by MTT. We also compare thedifference between the two groups;(2) Hepatic stellate cells were treated with the 10-8mol/lconcentration ofβ-estradiol andβ-estradiol nanoparticle for 48 hours,then the expression of TGF-β1 and CTGF mRNA were detected byRT-PCR. The difference was compared between the two groups;(3) Hepatic stellate cells were treated with the 10-8mol/l concentration ofβ-estradiol andβ-estradiol nanoparticle for 48 hours,then the expression ofα-SMA, TGF-β1, CTGF protein were detected byImmunocytochemistry. The difference was compared between the twogroups.Results (1) The effect ofβ-estradiol andβ-estradiol nanoparticleon the proliferation were confirmed. This was in the dose-dependent andtime-dependent manner;(2) We found that the effect ofβ-estradiol andβ-estradiolnanoparticle down-regulated the expression of TGF-β1 and CTGF mRNA.There was significant difference between the effect ofβ-estradiol andβ-estradiol nanoparticle.β-estradiol nanoparticle had better effect thanβ-estrodiol;(3) Theβ-estradiol andβ-estradiol nanoparticle down-regulated theexpression ofα-SMA, TGF-β1and CTGF in protein level. There wassignificant difference between the effect ofβ-estradiol andβ-estradiolnanoparticle.β-estradiol nanoparticle had better effect thanβ-estradiol.Conclusion (1) Bothβ-estradiol nanoparticle andβ-estradiol havethe function of suppressing the proliferation and activation of HSC,inhibitting the expression of pro-fibrogenic cytokine TGF-βand itsdownstream signaling CTGF;(2) Hepatic stellate cells were treated with the 10-8mol/l concentration ofβ-estradiol andβ-estradiol nanoparticle for 48 hours,β-estradiol nanoparticles has better effect thanβ-estradiol on theproliferation, activation and the expression of pro-fibrogenic cytokineTGF-βand it's downstream signaling CTGF of HSC;(3) It is one of the anti-fibrosis mechanisms thatβ-estradiolnanoparticle andβ-estradiol have the function of suppressing theproliferation and activation of HSC, inhibitting the expression ofpro-fibrogenic cytokine TGF-βand it's downstream signaling CTGF. |
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