Abstract To study the effect of Jiawei Huangqi Guizhi Decoction on gastrointestinal hormones and TGF-β3 signal pathways in rats with chronic atrophic gastritis (CAG). The model was created by methylnitrosoguanidine (MNNG) comprehensive method. After successful modeling, it was divided into three groups: model group (MC group), frolic acid group (AC group), modified Huangqi Guizhi Decoction high dose group (HH group), modified Huangqi Guizhi Decoction middle dose group (HM group), and modified Huangqi Guizhi Decoction low dose group (HL group). Gastric pathology was observed by HE staining. The levels of gastrin (GAS) and motilin (MTL) in rat serum were detected by ELISA assay. After HE staining, the histopathological sections were analyzed. Inflammatory factors infiltration and disorder of mucosal epithelial cells were found in the model group, which were improved to some extent after administration. According to the pathological chart analysis and score of rats in each group, compared with the model group, the gastric tissue damage of rats in each administration group has been improved in different degrees, among which the pathological scores of HH and HM groups were lower, and the corresponding damage degree was smaller. According to the test results of ELISA, Jiawei Huangqi Guizhi Decoction could reduce the contents of GAS, TGF-β3, and increase MTL abundance in the serum of rats, thus accelerating the apoptosis of tumor cells and inhibiting cancer. Jiawei Huangqi Guizhi Decoction played a positive role in preventing the occurrence of gastric cancer through reducing the concentrations of GAS and TGF-β3 in serum, and increasing the concentration of MLT in serum. This results provided a new treatment idea for CAG.

Resumo Fundamento: A doença cardiovascular é a principal causa de morte em todo o mundo. A apoptose mediada por hipóxia em cardiomiócitos é uma das principais causas de distúrbios cardiovasculares. O tratamento com a proteína do fator de crescimento endotelial vascular (VEGF, do inglês vascular endothelial growth factor) foi testado, mas as dificuldades operacionais limitaram seu uso. Entretanto, com os avanços da terapia gênica, aumentou o interesse na terapia gênica baseada no VEGF em doenças cardiovasculares. No entanto, o mecanismo preciso pelo qual a reposição de VEGF resgata os danos pós-hipóxia em cardiomiócitos não é conhecido. Objetivos: Investigar o efeito da expressão de VEGF121 pós-hipóxia utilizando cardiomiócitos de ratos neonatos. Métodos: Cardiomiócitos isolados de ratos neonatos foram utilizados para estabelecer um modelo in vitro de lesão cardíaca induzida por hipóxia. O efeito da superexpressão de VEGF, isolado ou em conjunto com inibidores de moléculas pequenas que têm como alvo os canais de cálcio, receptores sensíveis ao cálcio (CaSR, do inglês calcium-sensitive receptors) e calpaína, no crescimento e proliferação celular em lesão de cardiomiócitos induzidos por hipóxia, foram determinados com ensaio de MTT, coloração TUNEL, coloração com Anexina V/PI, lactato desidrogenase e atividade da caspase. Para análise estatística, um valor de p<0,05 foi considerado significativo. Resultados: Verificou-se que o efeito do VEGF121 foi mediado por CaSR e calpaína, mas não foi dependente dos canais de cálcio. Conclusões: Nossos resultados, mesmo em um ambiente in vitro, estabelecem as bases para uma validação futura e testes pré-clínicos da terapia gênica baseada em VEGF em doenças cardiovasculares.

Abstract Background: Cardiovascular disease is the major cause of death worldwide. Hypoxia-mediated apoptosis in cardiomyocytes is a major cause of cardiovascular disorders. Treatment with vascular endothelial growth factor (VEGF) protein has been tested but operational difficulties have limited its use. However, with the advancements of gene therapy, interest has risen in VEGF-based gene therapy in cardiovascular disorders. However, the precise mechanism by which VEGF replenishment rescues post-hypoxia damage in cardiomyocytes is not known. Objectives: To investigate the effect of post-hypoxia VEGF121 expression using neonatal rat cardiomyocytes. Methods: Cardiomyocytes isolated from neonatal rats were used to establish an in vitro model of hypoxia-induced cardiac injury. The effect of VEGF overexpression, alone or in combination with small-molecule inhibitors targeting calcium channel, calcium sensitive receptors (CaSR), and calpain on cell growth and proliferation on hypoxia-induced cardiomyocyte injury were determined using an MTT assay, TUNEL staining, Annexin V/PI staining, lactate dehydrogenase and caspase activity. For statistical analysis, a value of P<0.05 was considered to be significant. Results: The effect of VEGF121 was found to be mediated by CaSR and calpain but was not dependent on calcium channels. Conclusions: Our findings, even though using an in vitro setting, lay the foundation for future validation and pre-clinical testing of VEGF-based gene therapy in cardiovascular diseases.