Investigation of Efficacy and Mechanism of Zukamu Granules on Hypoxic Pulmonary Hypertension / 医药导报

Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Pterostilbeno Reduz o Estresse Oxidativo no Pulmão e no Ventrículo Direito Induzido por Infarto do Miocárdio Experimental / Pterostilbene Reduces Experimental Myocardial Infarction-Induced Oxidative Stress in Lung and Right Ventricle

Resumo Fundamento O pterostilbeno (PS), um composto polifenólico natural e antioxidante, surge como uma intervenção promissora para minimizar danos do infarto agudo do miocárdio (IAM). Objetivo Este estudo teve como objetivo avaliar o desempenho do PS na promoção da homeostase redox nos pulmões e no ventrículo direito (VD) de animais infartados. Métodos Ratos Wistar machos (60 dias de idade) foram randomizados em três grupos: SHAM, IAM (infarto) e IAM+PS (IAM + pterostilbeno). Sete dias após o procedimento de IAM, os ratos foram tratados com PS (100 mg/kg/dia) por gavagem por oito dias. Os animais foram depois sacrificados e os pulmões e VD foram coletados para análise do balanço redox (diferenças foram consideradas significativas quando p<0,05). Resultados Nossos resultados mostram que o IAM desencadeia a interrupção redox no VD e nos pulmões, o que pode contribuir para danos induzido pelo IAM nesses órgãos. Consistentemente, o PS mitigou o estresse oxidativo e restaurou as defesas antioxidantes (Glutationa - GSH nos pulmões: SHAM = 0,79 ± 0,07; IAM = 0,67 ± 0,05; IAM + PS = 0,86 ± 0,14; p<0,05), indicando seu papel protetor neste cenário. Conclusão Nosso trabalho evidencia o potencial do uso de PS como abordagem terapêutica adjuvante após IAM para proteção dos tecidos pulmonares e cardíacos direitos.

Abstract Background Pterostilbene (PS), a natural and antioxidant polyphenolic compound emerges as a promising intervention in improving the myocardial infarction (MI) damages. Objetives This study aimed to evaluate PS actions in promoting redox homeostasis in lungs and right ventricle (RV) of infarcted animals. Methods Male Wistar rats (60 day-old) were randomized into three groups: SHAM, MI (infarcted), and MI+PS (MI+pterostilbene). Seven days after MI procedure, rats were treated with PS (100 mg/kg/day) via gavage for eight days. Animals were euthanized and the lungs and RV were harvested for analyses of redox balance (Differences were considered significant when p<0.05). Results Our results show that MI triggers a redox disruption scenario in RV and lungs, which can contribute to MI-induced damage on these organs. Consistently, PS mitigated oxidative stress and restored antioxidant defenses (GSH in lungs: SHAM= 0.79±0.07; MI=0.67±0.05; MI+PS=0.86±0.14; p<0.05), indicating its protective role in this scenario. Conclusions Our work evidences the PS potential use as an adjuvant therapeutic approach after MI focusing on protecting pulmonary and right-sided heart tissues.

Effects of heat shock preconditioning on expressions of HSP60,HSP70 and iNOS in gastric mucosa of burned rats / 第三军医大学学报

Objective To observe the influence of heat shock preconditioning on the expressions of heat shock protein(HSP)60,70 and induced nitric oxidase synthase(iNOS)in gastric mucosa of severely burned rats and investigate the protective mechanism of burn-induced acute gastric mucosal lesion.Methods Ninety-six Wistar rats were divided into two groups:burn(B)and heat shock preconditioning before burn(HB).The extent of gastric mucosal lesions(UI)was evaluated grossly and histologically.HSP70 mRNA expression was determined by RT-PCR.Immunohistochemical method was used to analyze the protein expressions of iNOS,HSP60 and HSP70.Results Rats in B group were induced conspicuous gastric mucosal lesions,while UI in HB group was significantly lower.The expressions of HSP70 and HSP60 were significantly increased and the expression of iNOS was obviously decreased in HB group as compared with B group.Conclusion Heat shock preconditioning protects against acute gastric mucosal lesion caused by burn through enhancing the expressions of induced HSPs and reducing the iNOS expression.

Effects of insulin on nitric oxide synthase (NOS) activity and the expression of inducible NOS mRNA in calf aortic endothelial cells / 中华内分泌代谢杂志

Objective To observe nitric oxide synthase (NOS) activity and the expresssion of inducible NOS (iNOS) mRNA in cultured calf aortic endothelial cells treated with various concentrations of insulin. Methods Cultured calf aortic endothelial cells were incubated with different concentrations of insulin for 24 h. NOS activity was determined by colorimetry and iNOS mRNA was measured by semi-quantitative RT-PCR. Results NOS activity and the expression of mRNA in calf aortic endothelial cells at pharmacological concentration (10 -7 mol/L) of insulin were significantly increased than those at physiological concentration (10 -10 mol/L) of insulin (P

Immunohistochemical Expression of Placental Nitric Oxide Synthase in Preeclampsia and Normal Pregnancy / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to compare the expression of endothelial nitric oxide synthase in the placenta and umbilical cord of preeclamptic placenta with that of the normotensive placenta. METHOD: We compared placental endothelial nitric oxide synthase expression in preeclamptic (n=5) with in normal (n=5) pregnancies. Frozen sections of umbilical cords, chorionic plate vessels, and terminal villi were immunostained with a monoclonal endothelial nitric oxide synthase antibody. RESULTS: The age revaled no difference between control (28.1+4.2 years). and study group (26.1+4.7 years). The gestational age was statistically different between control (38.9+1.7 weeks) and study group (34.9+3.5 weeks). The neonatal body weight and placental weight were also statistically different between control (3060+528 g) and study group (2160 417 g). No difference in endothelial nitric oxide synthase immunostaining in the endothelium of the umbilical vessels and stem villous vessels was found between preeclamptic and normotensive pregnancies. In contrast, in the preeclamptic placental endothelial nitric oxide synthase immunostaining was seen in the terminal villous vessels. In the syncytiotrophoblast endothelial niric oxide synthase immunostaining appeared primary basal in location and diffuse in distribution in the preeclamptic placentas but primary apical in the normotensive placentas. CONCLUSION: Differences in endothelial nitric oxide synthase expression in terminal villous vessels and syncytiotrophblast may be a result of vascular alterations or damage that take place in the placenta in preeclampsia.