ABSTRACT
BACKGROUND:Buyang HuanwuDecoction is commonly used in clinical medicine in treatment of intracerebral hemorrhage. Previous studies have been found that it has excelent neuroprotective effect, can efficiently inhibit the apoptosis of nervecels. Autophagic activity is closely related to apoptosis of nerve cels. CXCR4-PI3K autophagy signaling pathway has been verified in clinic. However, the effect of Buyang HuanwuDecoction is poorly understood. There is no study on Beclin-1 in the neuroprotective studies ofBuyang HuanwuDecoction. OBJECTIVE:To explore the effects ofBuyang HuanwuDecoction on CXCR4-PI3K autophagy signaling pathway and Beclin-1 in rats with cerebral hemorrhage and related mechanisms. METHODS:According to Rosenberg method, a rat model of cerebral hemorrhage was replicated and intragastricaly administeredBuyang HuanwuDecoction. Western blot assay was used to measure Beclin-1 protein. Immunohistochemical method was utilized to detect the expression of PI3K, AKT, stromal cel derived factor 1 and CXCR-4 protein. TUNEL assay was applied to identify apoptosis. RESULTS AND CONCLUSION:(1) After administration,Buyang HuanwuDecoction could reduce the number of neuronal apoptosis in rats with intracerebral hemorrhage, up-regulate the expression of Beclin-1, PI3K, AKT, stromal cel derived factor 1, and CXCR-4 protein, and exert neuroprotective effect. (2)Buyang HuanwuDecoction could activate CXCR4-PI3K autophagy signal transduction pathway, both to stimulate autophagy and to regulate autophagy state, can inhibit apoptosis, and exert cerebral protective effect.
ABSTRACT
Objective To study the effect of paeonol (PAE) and PNS on the expression of transforming growth factor (TGF)- beta 1/ Smad2/3 pathway in rats with acute myocardial infarction (AMI), and the possible molecular mechanism thereof. Methods Model of AMI was made using left anterior descending coronary branch ligation. According to the inter?vention methods rats were divided into model group, PAE group (8 mg·kg-1), PNS group (40 mg·kg-1), PAE (4 mg·kg-1)+PNS (20 mg·kg-1) low dose group, PAE (8 mg·kg-1)+PNS (40 mg·kg-1) high dose group and captopril positive control group (10 mg · kg-1). Rats without ligation were used as Sham operation group. Left ventricular systolic blood pressure (LVSP), left ventricular diastolic pressure (LVEDP) and the maximum rise and fall rate (/dtmax DP) were detected after 28-day treat?ment. HE staining was used to observe changes of myocardial tissue. The protein expression levels of TGF-β1 and Smad2/3 were detected by Western blot assay. Results There were significant differences in parameters used for detecting treatment group and model group, formula group and single drug group, formula high dose group and formula low dose group (P <0.01). The model group showed pathological changes. All treatment groups showed different degrees of pathological improve?ment. There was the most significant improvement in formulae group and captopril group. Compared with the model group, TGF-β1 and Smad2/3 protein expressions were decreased in treatment group. The expression levels of TGF-β1 and Smad2/3 were significantly decreased in formula group than those of PAE group and PNS group, and lower levels in formula high dose group than those of formula low dose group (P<0.05). Conclusion Paeonol and PNS can inhibit the expressions of TGF-β/Smad 2/3 protein in rats with AMI, by blocking TGF-β/Smad pathway.
ABSTRACT
Objective To study the effect of paeonol (PAE) and panax notoginseny saponins (PNS) on the expressions of collagenⅠandⅢprotein and mRNA in rats with acute myocardial infarction (AMI), and to explore the molecular mecha?nism of improving myocardial fibrosis. Methods The rat model of AMI was made using the left anterior descending coro?nary branch ligation.According to the intervention rats were divided into model group, PAE (8 mg/kg) group, PNS (40 mg/kg) group, PAE (4 mg/kg)+PNS (20 mg/kg) group, PAE (8 mg/kg)+PNS (40 mg/kg) group and captopril positive control group (10 mg/kg). Sham operation group, only wear line without ligation. The left ventricular mass index (LVMI) was detected after treatment for 28 d. Masson staining was used to observe changes of myocardial fibrosis. Western blot assay and RT-PCR technique were used to detect protein and mRNA expression levels of collagenⅠandⅢ. Results The values of LVMI were increased in model group compared with those of sham operation group and treatment groups. Compared with PAE group and PNS group, values of LVMI were significantly decreased in PAE (4 mg/kg)+PNS (20 mg/kg) group and PAE (8 mg/kg)+PNS (40 mg/kg) group. There was a more significant decrease in formula high dose group (P < 0.01). The model group showed pathological change. There were different degrees of improvement in pathological structure in all treatment groups, more sig?nificant improvement was found in formula low dose group, formula high dose group and captopril positive control group. There were different degrees of increase in expressions of collagenⅠandⅢprotein and mRNA in model group compared with those of sham operation group and treatment groups. Compared with PAE group and PNS group, the protein and mRNA expression levels of collagenⅠandⅢwere significantly decreased in formula low dose group and formula high dose group,more significant decreased was found in formula high dose group (P<0.05). Conclusion Compound of paeonol and PNS can improve myocardial fibrosis in myocardial infarction rats, which may be related with reduced expressions of collagenⅠandⅢprotein and mRNA.