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Objective To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage. Methods Sixty SD rat aged 9–12 weeks were chosen and divided into the control group, model group and simvastatin-treated group randomly with 20 rats in each group. Rats in the model group and simvastatin-treated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model, while rats in the control group were treated with the same amount of normal saline. Then, rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling. Rats in the three groups were given nerve dysfunction score (NDS) and wet-dry weighting method was used to detect the brain water content (BWC) of brain tissues around the lesion of the rats. Then Nissl staining was conducted and the undamaged neurons were counted. Immunohistochemical SP method was applied to count the number of NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions, and the immuno fluorescence method was employed to determine the expression levels of NF-κB, TLR4 and IL-1β proteins. Results The NDS results of the simvastatin-treated group at all time points were all significantly higher than those of the model group ( P < 0.05); the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods ( P < 0.05); the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group ( P < 0.05); seven days after treatment, the number of the NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group ( P < 0.05), and its expression levels of NF-κB, TLR4 and IL-1β protein were also significantly lower than those of the model group ( P < 0.05). Conclusions Simvastatin can inhibit the expressions of NF-κB, TLR4 and IL-1β proteins in rats with cerebral hemorrhage, and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses. [ABSTRACT FROM AUTHOR]

Objective To explore the protective effects of ginseng mixture on myocardial fibrosis (MF) in rats. Methods A total of 60 Wistar rats were randomly divided into control group without modeling operation, and another 4 groups using subcutaneous injections of isopropyl adrenaline for 10 d to set up the MF model: model group with saline lavage treatment after modeling, captopril group with captopril lavage, ginseng mixture group A and group B with low and high dose mixture treatment respectively. After treatment for 14 d, abdominal aorta and myocardial tissue were extracted to observe the pathological morphological changes and heart weight index in each group. Results The left ventricular weight and heart heavy index of captopril group and group B were significantly lower than that of model group and group A ( P <0.05); Model group and group A showed a higher hydroxyproline (Hyp) content in myocardial tissue than the control group and lower catalase (CAT) activity than control group ( P <0.05); captopril group and group B showed a lower Hyp content and higher CAT activity compared with group A and model group ( P <0.05), a significantly lower level of serum glutathione peroxidase (GSH-PX) and CAT and a higher level of serum creatine kinase, lactate dehydrogenase and H 2 O 2 in model group and group A were observed compared with the control group ( P <0.05). A higher level of GSH-PX and CAT and a lower level of creatine kinase, lactate dehydrogenase and H 2 O 2 in captopril group and group B were observed compared with group A and model group ( P <0.05); and histopathological examination showed that in captopril group and group B, secretion of collagen fiber was significantly inhibited and myocardial injury was significantly lighter than that of model group. Conclusions Ginseng mixture plays a protective effect on myocardium by inhibiting antioxidant process of MF. [ABSTRACT FROM AUTHOR]

A potential link between tissue-type transglutaminase (tTG) and cardiac hypertrophy was suggested recently. However, whether tTG is implicated in hypertrophic agonist-induced cardiac hypertrophy is not yet known. The purpose of this study was to investigate the effects of tTG on cardiomyocyte hypertrophy induced by endothelin (ET) 1. Real-time quantitative RT-PCR and Western blot analysis demonstrated that ET-1 increased the expression of tTG mRNA and protein in cardiomyocytes by activating ET(A) receptors. ET-1 failed to cause increases in cell size and [(3)H]leucine uptake, sarcomere reorganization, and gene induction of the atrial natriuretic factor when cardiomyocytes were treated with monodansylcadaverine, a competitive inhibitor of tTG. Furthermore, the effects of ET-1 on multifunctional activities of tTG were determined by evaluating the incorporation of [(3)H]putrescine into N,N'-dimethylated casein and charcoal absorption, respectively. The results showed that ET-1 did not influence the basal transglutaminase activity of cardiomyocytes but significantly inhibited the 0.1-mmol/L Ca(2+)-stimulated transglutaminase activity. Otherwise, ET-1 elevated the activity of GTPase in a concentration- and time-dependent manner. In vivo, right ventricular hypertrophy induced by 2 weeks of chronic hypoxia was depressed by the tTG inhibitor cystamine (10 to 30 mg/kg, 2 times per day, IP) in a dose-dependent manner. Taken together, our data strongly supported the notion that tTG may act as a positive regulator of the hypertrophic program in response to ET-1. This is probably attributable to the signaling activity of tTG rather than transglutaminase activity. [ABSTRACT FROM AUTHOR]