RESUMO
BACKGROUND: In the hypothalamic paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHRs), the expression of the testis-specific protein, Y-encoded-like 2 (TSPYL2) and the phosphorylation level of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) are higher comparing with the normotensive Wistar Kyoto rats (WKY). But how they are involved in hypertension remains unclear. TSPYL2 may interact with JAK2/STAT3 in PVN to sustain high blood pressure during hypertension. METHODS: Knockdown of TSPYL2 via adeno-associated virus (AAV) carrying shRNA was conducted through bilateral microinjection into the PVN of SHR and WKY rats. JAK2/STAT3 inhibition was achieved by intraperitoneally or PVN injection of AG490 into the SHRs. Blood pressure (BP), plasma norepinephrine (NE), PVN inflammatory response, and PVN oxidative stress were measured. RESULTS: TSPYL2 knock-down in the PVN of SHRs but not WKYs led to reduced BP and plasma NE, deactivation of JAK2/STAT3, decreased expression of pro-inflammatory cytokine IL-1ß, and increased expression of anti-inflammatory cytokine IL-10 in the PVN. Meanwhile, AG490 administrated in both ways reduced the BP in the SHRs and deactivated JAK2/STAT3 but failed to change the expression of TSPYL2 in PVN. AG490 also downregulated expression of IL-1ß and upregulated expression of IL-10. Both knockdown of TSPYL2 and inhibition of JAK2/STAT3 can reduce the oxidative stress in the PVN of SHRs. CONCLUSION: JAK2/STAT3 is regulated by TSPYL2 in the PVN of SHRs, and PVN TSPYL2/JAK2/STAT3 is essential for maintaining high BP in hypertensive rats, making it a potential therapeutic target for hypertension.
Assuntos
Pressão Sanguínea , Hipertensão , Janus Quinase 2 , Núcleo Hipotalâmico Paraventricular , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Masculino , Ratos , Modelos Animais de Doenças , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Janus Quinase 2/metabolismo , Norepinefrina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/enzimologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Fosforilação , Fator de Transcrição STAT3/metabolismo , Tirfostinas/farmacologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismoRESUMO
Inula japonica was used as the research object, "3414" fertilization experiment were conducted to study the effects of nitrogen,phosphorus and potassium formula fertilizer on the growth and chemical composition content of I. japonica. The characteristics of fertilizer requirement were preliminarily revealed and the study provided fertilization guidance for artificial cultivation of I. japonica. The results showed that different nitrogen,phosphorus and potassium formula fertilizers had significant effects on plant morphology,physiological and biochemical indexes,dry matter accumulation and chemical composition content. The growth indexes and chemical components of I. japonica showed an upward trend with the increase of fertilization amount,especially the nitrogen fertilizer was the most significant. The indicators were analyzed by membership function. After comprehensive evaluation,the optimal nitrogen,phosphorus and potassium formula fertilization level was N3 P2 K2,namely high level nitrogen fertilizer,medium level phosphorus fertilizer and potassium fertilizer. I. japonica is a high fertilizer demand plant,and the rational fertilization scheme is " applying nitrogen fertilizer again and applying phosphorus and potassium fertilizer properly".