The effects of sympathetic neurotransmitters and adrenergic receptors on liver fibrosis in murine schistosomiasis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of sympathetic neurotransmitters and adrenergic receptors on liver fibrosis in murine schistosomiasis.</p><p><b>METHODS</b>Mice were infestated with schistosoma by means of pasting cercariae on their abdomens. Thirty mice were randomly divided into a control group and a model group. Hematoxylin eosin and Van Gieson staining were used to view the histopathology of their livers. Immunofluorescence histochemistry and laser scanning confocal fluorescence microscopy were used to measure the a1A and beta2 adrenergic receptors in livers of the two groups of mice. High performance liquid chromatography-electrochemical detector (HPLC-ECD) was used to determine the concentration of norepinephrine (NE) and dopamine (DA) in the plasma of the mice.</p><p><b>RESULTS</b>Immunofluorescence histochemistry showed that a1A and beta2 receptors were present in hepatocytes and hepatic sinusoids of the livers of the mice of the two groups, but there were many more in the livers of the schistosoma infected mice (t=-2.888; t=-6.648) (P<0.05). The results of HPLC-ECD showed that the levels of NE and DA in the model group were higher than those of the control group (t=-3.372; t=-4.428) (P<0.05).</p><p><b>CONCLUSION</b>Sympathetic neurotransmitters and adrenergic receptors may participate in liver fibrogenesis in mice infected with schistosoma.</p>

Effects of anandamide on the activation and proliferation of hepatic stellate cells through cannabinoid-2 receptors / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effects of endogenous cannabinoid anandamide (AEA) and its putative endocannabinoid receptors (CBR) on the activation and proliferation of hepatic stellate cells (HSC) and to study the role played by AEA during liver fibrosis.</p><p><b>METHODS</b>By using immunofluorescence and cell culture, the expression of CBR 1 and 2 in the PDGF-stimulated HSCs was investigated. By using PCR and Western-blot, the effects of 10, 20mumol/L AEA and CBR2 antagonist AM630 on the cultured and activated HSC were observed. Methyl thiazolyl tetrazolium and flow cytometry were used to investigate whether AEA induces growth inhibition or apoptosis in the activated HSCs.</p><p><b>RESULTS</b>Both CBR1 and CBR2 receptors were detectable in cultured HSCs with a higher level of CBR2 than CBR1 (F = 116.797, P less than 0.01). When HSCs were stimulated by PDGF, the expression of CBR2 receptors was significantly enhanced (F = 7.878, P less than 0.05). HSC proliferation was dose-dependently inhibited by 10, 20, and 50micromol/L AEA, with the rates of 7.12%+/-0.34%, 12.52%+/-0.78%, 80.13%+/-1.57% respectively (F = 533.41, P less than 0.01). However, it did not induce apoptosis, but necrosis. The expressions of alpha-SMA, TGFb1, a1(I), a1(III) and TIMP-1 were significantly suppressed by 20micromol/L AEA, but CBR2 antagonist AM630 reversed this suppressor action of AEA.</p><p><b>CONCLUSIONS</b>AEA may inhibit activation and proliferation of HSCs; CBR2 receptors mediate AEA-induced inhibitory action on the activation of HSCs. This CBR2 receptor-mediated action and AEA on HSCs could be used as a therapeutic target against liver fibrosis.</p>