Objective To investigate the effects and signal transduction pathway of vasonatrin peptide(VNP),a novel man-made natriuretic peptide,on hepatic fibrosis.Methods Mice were injec ted with carbon tetrachloride(CCl4)for 12 weeks,with or without VNP treatment in the last 6 weeks.HE staining and Sirius red staining were performed to evaluate the status of hepatic fibrosis.In vitro after treatment of VNP,and DNA and collagen synthesis of cultured HSC-T6 hepatic stellate cells were assessed by[3H]-thymidine and[3H]proline incorporation,respectively.The signaling pathway involved was identified by radioimmunoassay to detect the levels of intracellular cGMP,and by mimicking experiments using 8-br-cGMP(a membrane-permeable cGMP analog).Blocking experi ments were performed using HS-142-1,an antagonist of guanylyl cyclase-coupled natriuretic peptide receptor(NPR),or KT-5823,the cGMP-dependent protein kinase(PKG)inhibitor.Results VNP markedly alleviated CCl4-induced liver fibrosis in mice.In vitro,HSC-T6 cells demonstrated a dosedependent reduction of DNA and collagen synthesis in the presence of VNP.In addition,VNP significantly increased intracellular levels of cGMP.The effects of VNP were mimicked by 8-br-cGMP,but they were inhibited by HS-142-1,or KT-5823.Conclusion VNP ameliorated liver fibrosis by inhibiting collagen production from hepatic stellate cells via guanylyl cyclase-coupled NPR/cGMP/PKG signal pathway,indicating that VNP might be a new effective agent in the treatment of liver fibrosis.

Stroke has become one of the main causes of death in China, and ischemic stroke is the most common type. At the same time, the prevalence of chronic kidney disease (CKD) is also increasing, and there are many similar risk factors with ischemic stroke. More and more studies have shown that CKD increases the incidence, severity and risk of poor outcome of ischemic stroke, but the specific mechanism of its interaction is not completely clear. For ischemic stroke patients with CKD, the most effective treatment and prevention measures are lack of sufficient evidence. This article reviews the relationship between CKD and ischemic stroke, as well as the treatment and prevention.

Objective To investigate the effect and mechanism of astragaloside Ⅳ(AS-Ⅳ) activating ROCK/JNK to regulate autophagy in improving isoproterenol (ISO) induced myocardial fibrosis (MF) in mice. Methods The mice were randomly divided into control operation group (Control group), ISO induced myocardial fibrosis group (MF group), AS-Ⅳ treatment group (AS-Ⅳ group) and combination group of astragaloside IV and Y-33075 (ROCK inhibitor) (astragaloside IV+Y-33075 group). After repeated administration for 30 days. The serum levels of LDH, BNP, CTGF in each group were detected. The cardiac function was detected by ultrasound. Myocardial structure and tissue fibrosis degree in each group were detected by Sirius Red and Masson staining. Oxidative stress (ROS) levels in myocardial tissue of each group were detected by DHE staining and the expression of ROCK, JNK, Atg5, Beclin 1, and LC3 Ⅰ/Ⅱ in myocardial tissue were detected by Western blotting. Results Compared with AS-Ⅳ group, the EF value of AS-Ⅳ+Y-33075 group decreased and the degree of myocardial fibrosis increased (P<0.05). The serum level of LDH, BNP, CTGF increased and the level of ROS in myocardial tissue increased while the expression of ROCK, JNK, Atg5, Beclin 1, LC3 Ⅰ/Ⅱ decreased (P<0.05). Y-33075 could block the protective effect of AS-Ⅳ on myocardial injury induced by MF and inhibit the regulation of AS-Ⅳ on ROCK and JNK. Conclusion AS-Ⅳ could attenuate myocardial fibrosis in mice by activating ROCK/JNK signal and promoting autophagy.