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BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P＜0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.
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Objective To detect the expression of Nrf2 in mice with viral myocarditis and to investigate the changes and effects of Nrf2 after puerarin (Pue) treatment.Methods A total of 130 BALB/C male mice aged 4 weeks were randomly divided into control group,VMC group,Nrf2 activator group and Pue group (20 mice in each group) with different concentrations.The models were made with Coxsackie B3 virus (CVB3).The mice were sacrificed on day 0,4,7,14 and 28 respectively,and blood and myocardial samples were harvested.Cardiomyocyte apoptosis was detected by flow cytometry.The expression changes of Nrf2,HO-1,Fas,TGF-beta 1 mRNA were detected by real-time PCR and Western blot respectively.Statistical software SPSS19.0 was used to analyze the results.The measurement data was expressed mean ± standard deviation.The paired samples were tested with mean t test.The group data were analyzed with two-way ANOVA.A P value of less than 0.05 was considered to indicate statistical significance.Correlation analysis was performed with Spearman's correlation test.Results Nrf2 mRNA and Nrf2 protein were expressed in all groups.The correlations between Nrf2 and HO-1,Fas and TGF-beta-1 were analyzed according to CPDT or Pue,and the results were consistent with each other.It showed that the relationship between Nrf2 and HO-1,Fas and TGF-beta-1 did not change with intervention measures.The transcription and protein expression of HO1 in CPDT and Pue groups were significantly increased,and were positively correlated with Nrf2 (r =0.969,P ＜0.01).At a certain dose gradient (＜ 45 mg/kg),the transcription and protein expression of HO-1 were dose-dependent;the decreased cardiomyocyte apoptosis was observed in both CPDT and Pue group,while Nrf2 and Fas were negatively correlated (r =-0.968,P ＜ 0.01);at a certain dose gradient,the expression of TGF-beta 1 in CPDT and Pue group decreased with the increase of dose,and Nrf2 and TGF-beta 1 were negatively correlated (r =-0.753,P ＜ 0.01).Conclusion The increased expression of Nrf2 in VMC is involved in the occurrence and development of VMC.Nrf2 has antioxidant effect in VMC by up-regulating the antioxidant enzyme HO-1,has the anti-myocardial APO effect by inhibiting the Fas/FasL signaling pathway,and inhibits myocardial fibrosis by suppressing the expression of TGF-beta 1 protein and transcription.The therapeutic effect of Pue on VMC is to activate Nrf2 to produce antioxidant,anti-apoptotic and anti-fibrotic effects.
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Objective To investigate the effect of simvastatin on gene expression of L-type calcium channels(LCCs) of myocardial cells in BALB/c mice infected by coxsackievirus B3(CVB3) so as to study the therapeutic effect of simvastatin on viral myocarditis.Methods Sixty male BALB/c mice were divided into five groups randomly(n=12).Mice in viral control group and three groups of oral administration of simvastatin(10,30 and 90 mg?kg-1)were inoculated intrapritoneally with 0.2 mL of CVB3(Nancy strain).Mice in normal control group were inoculated intrapritoneally with 0.2 mL Eagle's solution.The heart samples of all the mice were obtained for hispathological study and detection of myocardial LCCs alpha1 subunits mRNA expression by semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR).Results In viral control group,the mononuclear inflamematory infiltrate was focal or diffuse in myocardium of mice,severe hearts revealed a large area of myocardial necrosis.The degree of inflammatory cell infiltrate and area of necrosis were significantly less in simvastatin groups as compared with viral control group.The myocardial LCCs alpha1 subunits mRNA expression by semi-quantitative RT-PCR in normal control group was much lower than that in viral control group(0.06?0.01 vs 1.37?0.32,P
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Objective To study the expressions of survivin and caspase-9 in human primary hepatocellular carcinoma(HCC) tissues and their relationship with apoptosis.Methods Immunohistochemical staining was uesed to detect the expressions of survivin and caspase-9 in paraffin sections of 96 cases including 42 HCC tissues,42 paired adjacent noncancerous tissues and 12 normal liver tissues. Apoptosis was detected by TUNEL.Results No immunoreactivity of survivin was seen in normal liver tissues.The positive rates of survivin in HCC and paired adjacent noncancerous tissues were 73.81% and 4.76%,respectively,there was significant difference between two groups(P0.05).The expressions of survivin and caspase-9 in HCC tissues were not associated with age,sex and the size of tumor,but they were directly associated with tumor histological grade and metastasis.Conclusion High expression of survivin in HCC may inhibit apoptosis through depressing the expression of caspase-9,and it is an indicator of independent poor prognosis.