Effect of oxymatrine on the p38 mitogen-activated protein kinases signalling pathway in rats with CCl4 induced hepatic fibrosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have suggested that p38 mitogen-activated protein kinases (MAPK) signalling pathway plays an important role in hepatic fibrosis. This study explored the antifibrotic effect of oxymatrine on tetrachloromethane induced liver fibrosis in rats and its modulation on the p38 MAPK signalling pathway.</p><p><b>METHODS</b>One hundred and twenty healthy male Sprague-Dawley rats were randomly assigned to six groups: normal (n = 20), induced fibrosis (n = 20), colchicine (n = 20) and three treatment groups of oxymatrine (n = 20 x 3). We obesrved changes in deposition of collagen, hyaluronic acid (HA), laminin (LN), collagen type IV (CIV), procollagen III (PCIII) and hydroxyproline (Hyp), a-smooth muscle actin (alpha-SMA) and phosphor-p38 (pp38).</p><p><b>RESULTS</b>The relative indicators of changes in histopathology, HA, LN, CIV, PCIII, Hyp, alpha-SMA and pp38 were raised significantly in the induced fibrosis group (P < 0.01 vs normal group). The semiquantitative hepatic fibrosis staging scores of middle dose group and high dose group were decreased (P < 0.05 and P < 0.01 respectively vs the induced fibrosis group), as was the average area of collagen in rats' liver, the concentrations of serum HA, LN, CIV, PCIII and liver tissue homogenate Hyp. The gene expression of alpha-SMA mRNA was considerably decreased in the treated animals, as was the protein espression of pp38 protein.</p><p><b>CONCLUSIONS</b>Oxymatrine is effective in reducing the production and deposition of collagen in the liver tissue of experimental rats in ways which relate to modulating the fibrogenic signal transduction via p38 MAPK signalling pathway.</p>

Antiinflammatory and immunoregulatory effects of total glucosides of Yupingfeng powder / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Yupingfeng, a traditional Chinese complex prescription, has been used efficaciously in China for the cure and prevention of inflammatory diseases related to immunodeficiency such as allergic rhinitis and chronic bronchitis. However, the active components of this prescription remain unclear. The present study focused on investigating the antiinflammatory and immunoregulatory effects of the glucosidic extract from Yupingfeng.</p><p><b>METHODS</b>We tested animal models for ear swelling induced by dimethylbenzene in mice; palm swelling induced by carregeenin and granuloma induced by cotton pellet in rats; level of haemolysin, antibody generation by the splenic cells, delayed hypersensitivity and T cell subsets in spleen of immunosuppressed mice.</p><p><b>RESULTS</b>Glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg significantly inhibited mice's ear swelling induced by dimethylbenzene. Similarly glucosidic extract of 16 mg/kg, 32 mg/kg and 64 mg/kg inhibited rats' palm swelling induced by carregeenin and granuloma induced by cotton pellet. Glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg improved the IgM level in serum and level of haemolysin in splenocytes in mice immunosuppressed by cyclophosphamide. Delayed hypersensitivity in mice suppressed by cyclophosphamide was enhanced by glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg. These results suggested that Yupingfeng could recover humoral and cellular immune function in mice with immunosuppression. Glucosidic extract of 48 mg/kg and 96 mg/kg significantly resisted the immunosuppressive mice ear swelling and maintained it at nearly normal level. The enhanced, delayed hypersensitivity actions of glucosidic extract, suppressed by cyclophosphamide, might be brought about by inducing TH cell and regulating T lymphocytes subset.</p><p><b>CONCLUSIONS</b>The glucosidic extract from Yupingfeng has antiinflammatory and immunoregulation action, suggesting that these glucosides are the principal active components of the traditional Chinese prescription Yupingfeng.</p>

Effects of losartan and simvastatin on collagen content, myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overload rat hearts / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of simvastatin(Sim) and losartan(Los) on cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overloaded rat hearts.</p><p><b>METHODS</b>The pressure overload model was induced by descending aortic constriction (DAC) in rats. SD rats were randomized into 6 groups (n = 20 each): normol control group, control sham group, DAC group, Los group (DAC + Los, 5 mg/kg), Sim group (DAC + Sim, 2 mg/kg), Los + Sim group (DAC + Los + Sim, Los 5 mg/kg, Sim 2 mg/kg). Water, Los or Sim drug was administrated by gavage daily beginning from day 5 after operation for 30 days. Collagen was measured on Masson stained myocardial sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in left ventricle were detected by RT-PCR.</p><p><b>RESULTS</b>Collagen volume fraction (CVF) in DAC group was significantly higher than the normal control and sham groups (P < 0.01) which could be significantly reduced by Los and Sim (P < 0.05), especially in DAC + Los + Sim group (P < 0.01). The levels of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in DAC group than in normal control and sham groups (P < 0.01). Treatment Sim and Los alone and especially in combination significantly decreased the TIMP-1 mRNA, TIMP-2 mRNA expressions (P < 0.01) while MMP-2 mRNA, MMP-9 mRNA levels remained unchanged (P > 0.05).</p><p><b>CONCLUSION</b>Upregulation of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial fibrosis in this model, Sim and Los significantly inhibited myocardial fibrosis possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in this model.</p>

Interactions between angiotensin converting enzyme inhibitors and aspirin / 中国药理学通报

Both aspirin and angiotensin converting enzyme (ACE) inhibitors are often used concomitantly in patients with cardiovascular disease. The safety of the combination has been questioned. The potential antagonistic interactions between ACE inhibitors and aspirin has become the focus of both increasing research and intense debate, with conflicting conclusions having been reported in the literature. We reviewed systematically available literature on the interactions between ACE inhibitors and aspirin in hypertension, acute myocardial infarction and congestive heart failure and found that further trials are needed to shed light on the effects and mechanism of interaction between these drugs.

Effects and mechanism of interactions between captopril and aspirin on injured myocardial cells from neonate rats / 中国药理学通报

AIM: To observe the effects of interactions between captopril and aspirin on injured myocardial cells from neonate rats and its mechanism. METHODS: The injury model of cultured neonatal rat myocardial cells was developed. The activity of lactate dehydrogenase (LDH) and the level of nitric oxide (NO) were measured by LDH kits and Griess reagent respectively, the intracellular free calcium concentrations were measured with Fura-2/AM. RESULTS: Both captopril and aspirin could reduce obviously the activity of LDH and increase the level of NO in medium, but their combination produced significant antagonistic interactions. Captopril reduced obviously the intracellular free calcium concentrations in the injury model, but aspirin alone or in combination with captopril significantly increased it. CONCLUSION: Captopril and aspirin combination produced significant antagonistic interactions, the effects may be related to its actions of reducing the production of NO and increasing the intracellular free calcium concentrations.