RESUMEN
OBJECTIVE@#To investigate the potential antifibrotic mechanisms of Chinese medicine Ganshuang Granules (, GSG) and to provide clinical therapeutic evidence of its effects.@*METHODS@#A cirrhotic mouse model was established by intraperitoneally injecting a mixture of CCl (40%) and oil (60%) at 0.2 mL per 100 g of body weight twice a week for 12 weeks. After 12-week modeling, GSG was intragastric administrated to the mice for 2 weeks, and the mice were divided into low-, medium- and high-dose groups at doses of 1, 2 and 4 g/(kg·day), respectively. Liver morphology changes were observed using Masson's trichrome staining and B-ultrasound. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hyaluronic acid (HA) in serum were detected using an automatic biochemistry analyzer. The expressions of desmin, smooth muscle actin (SMA) and Foxp3 in liver were detected by immunoflfluorescence. The regulatory T cell (Treg) frequency was determined through flflow cytometry analysis. Collagen-I, SMA, IL-6, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and transforming growth factor β1 (TGF-β1) expression levels were measured using quantitative polymerase chain reaction (qPCR).@*RESULTS@#Masson's staining result showed fewer pseudolobule structures and fibrous connective tissue in the GSG-treatment groups than in the spontaneous recovery group. Ultrasonography showed that GSG treatment reduced the number of punctate hyperechoic lesions in mice cirrhotic livers. The serum ALT, AST, HA levels were significantly ameliorated by GSG treatment (ALT: F=8.104, P=0.000; AST: F=7.078, P=0.002; and HA: F=7.621, P=0.001). The expression levels of collagen-I and SMA in the cirrhotic livers were also attenuated by GSG treatment (collagen-I: F=3.938, P=0.011; SMA: F=4.115, P=0.009). Tregs, which were elevated in the fibrotic livers, were suppressed by GSG treatment (F=8.268, P=0.001). The expressions of IL-6, TNF-α and IL-1β increased, and TGF-β levels decreased in the cirrhotic livers after GSG treatment (IL-6: F=5.457, P=0.004; TNF-α: F=6.023, P=0.002; IL-1β: F=6.658, P=0.001; and TGF-β1: F=11.239, P=0.000).@*CONCLUSIONS@#GSG promoted the resolution/regression of cirrhosis and restored liver functions in part by suppressing Treg cell differentiation, which may be mediated by hepatic stellate cells.
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Animales , Masculino , Ratones , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Células Estrelladas Hepáticas , Cirrosis Hepática Experimental , Quimioterapia , Alergia e Inmunología , Ratones Endogámicos BALB C , Linfocitos T ReguladoresRESUMEN
<p><b>OBJECTIVE</b>To study the possible pathogenic mechanism of liver injury in type 2 diabetes mellitus (T2DM) and the intervening effect of puerarin on it.</p><p><b>METHODS</b>Mice with T2DM (KKAy) were randomly divided into two groups, the model group and the puerarin group. And the C57BL/J mice of the same age were set up as normal controls. They were sacrificed at 28 weeks old for observing serum fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST) by automatic biochemistry; liver cell apoptosis by flow cytometry; pathomorphology by electron microscope; and mRNA expressions of bcl-2 and bax genes by RT-PCR; as well as the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na(+)-K(+)-ATPase; and content of malondialdehyde (MDA) in liver tissue by spectrophotometer.</p><p><b>RESULTS</b>In KKAy mice, blood levels of FBG, TG, TC, ALT, AST and liver cell apoptosis rate were higher; the bax mRNA expression was higher and bcl-2 mRNA was lower markedly; the activities of SOD, GSH-Px, Na(+)-K(+)-ATPase in liver tissue were lower, and MDA content was higher than those in the normal control significantly (all P <0.01). Besides, mitochondria swelling and damage were found in liver tissue. While in the puerarin group after treatment, all the above-mentioned changes were alleviated to some extent.</p><p><b>CONCLUSIONS</b>Obvious liver injury emerges in KKAy mice. Puerarin shows a protective effect on the T2DM caused oxidative damage by way of up-regulating bcl-2 to inhibit oxidative stress, and improving the energy metabolic dysfunction in liver of mice.</p>
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Animales , Masculino , Ratones , Diabetes Mellitus Experimental , Quimioterapia , Patología , Diabetes Mellitus Tipo 2 , Quimioterapia , Patología , Isoflavonas , Usos Terapéuticos , Hígado , Metabolismo , Hepatopatías , Quimioterapia , Ratones Endogámicos C57BL , Mitocondrias Hepáticas , Patología , Estrés Oxidativo , Fitoterapia , Proteínas Proto-Oncogénicas , Metabolismo , Proteínas Proto-Oncogénicas c-bcl-2RESUMEN
<p><b>OBJECTIVE</b>To study apoptosis-regulating cytokines and apoptosis on focal cerebral ischemia and reperfusion in rats treated with Xinnao Shutong capsule.</p><p><b>METHOD</b>Rat models of focal cerebral ischemia and reperfusion were established by thread ligation in middle cerebral artery occlusions (MCAO). After 24 hours, the brains were removed to detect changes of protein expression of Bax, Bcl-2, Fas, Fas-L and caspase-3 by immuno-hisochemistry, and apoptosis of cortical neurons by TUNEL RESULT: Compared to control, brain cortex have decreasing the protein expression of Bcl-2 and the ratio of Bcl-2/Bax, increasing the protein expression of Bax, Fas, Fas-L and caspase-3 of ischemia and reperfusion models group (P < 0.01). Xinnao Shutong capsule group could increase the protein expression of Bcl-2 and the ratio of Bcl-2/Bax, and obviously decrease the protein expression of Bax, Fas, Fas-L and caspase-3, then reduce the number of apoptotic cells of cortex (P < 0.01).</p><p><b>CONCLUSION</b>Xinnao Shutong capsule protect injured rat brain tissue, may be related to decrease neuronal apoptosis and adjusted protein expression of apoptosis-regulating cytokines.</p>
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Animales , Femenino , Humanos , Masculino , Ratas , Apoptosis , Proteínas Reguladoras de la Apoptosis , Genética , Metabolismo , Isquemia Encefálica , Quimioterapia , Metabolismo , Cirugía General , Cápsulas , Infarto Cerebral , Quimioterapia , Metabolismo , Cirugía General , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Expresión Génica , Distribución Aleatoria , Ratas Sprague-Dawley , ReperfusiónRESUMEN
<p><b>OBJECTIVE</b>To study the effect of Xinnao Shutong capsule (XNST) on energy metabolism dysfunction, free radical injury and inflammatic factors in the course of acute cerebral ischemic damage, and try to reveal the mechanism of the protection against ischemia.</p><p><b>METHOD</b>60 male Wistar rats weighing 280 - 320 g were randomly divided into five groups: normal, sham operation, model, XNST treatment( XNST-T) , and Western medicine treatment (WM-T) group. Acute multi-infarct model in rats was induced by injecting the embolus of blood powder through the right external carotid artery (ECA) into the internal carotid artery (ICA). At 72 hours after ischemia, morphologic change and the express of tumor necrosis factor-alpha (TNF-alpha) and interleukin -1beta ( IL-1beta) in hippocampus CAl section and cortex were observed, biochemical criterions including the activity of Na+ -K+ -ATPase, lactate dehydrogenase (LDH), superoxide dismutase (SOD), and the content of malondialdehyde (MDA) in hippocampus were examined.</p><p><b>RESULT</b>The morphologic change of hippocampus and cortex in both XNST-T and WM-T groups was milder than that in model group. The activity of Na+ -K+ -ATPase, LDH and SOD in hippocampus were all significantly decreased in model group (P <0. 01), and elevated in XNST group (P <0. 01) as well as in WM-T group (P <0. 01). The content of MDA in hippocampus was significantly increased in model group (P <0. 05), and was reduced in XNST group (P <0. 05) as well as in WM-T group (P <0. 01).</p><p><b>CONCLUSION</b>The results reveal that XNST has the protective effect against cerebral ischemic injury. And its possible mechanism is that XNST can prevent the upper pathological process.</p>