ABSTRACT
OBJECTIVE To study the improvement effects of arbutin on myocardial fibrosis （MF） model rats and its mechanism. METHODS The network pharmacology was used to predict the potential target of arbutin in improving MF and molecular docking was used to validated. Totally 50 SD rats were given isoprenaline subcutaneously （5 mg/kg， once a day， for 14 consecutive days） to induce the MF model. Modeled rats were randomly divided into model group， captopril group （9 mg/kg）， arbutin low-dose， medium-dose and high-dose groups （50， 100， 200 mg/kg）， with 10 rats in each group. Another 10 healthy rats were included as normal group. Each group was given the corresponding drugs， once a day， for 28 consecutive days. Twenty-four hours after the final administration， electrocardiograms and heart-related indexes [heart weight index （HWI）， left ventricular weight index （LVWI）] of rats were detected； the levels of creatine kinase （CK）， lactate dehydrogenase （LDH）， N-terminal pro-brain natriuretic peptide （NT-proBNP） and type Ⅰ collagen （Col Ⅰ） and Col Ⅲ were detected in myocardial tissue of rats； the pathological changes of myocardial tissue were observed， and protein and mRNA expressions of adenosine deaminase （ADA） and adenosine kinase （ADK） were detected in the myocardial tissue of rats. RESULTS The results of network pharmacology showed that the main targets of arbutin improving MF were ADA and ADK. The results of molecular docking showed that arbutin bind stably with ADA and ADK. The results of experimental verification showed that compared with model group， the amplitude of ST and T waves in electrocardiogram were improved in administration groups， and the symptoms of atrial flutter were alleviated； HWI （except for arbutin medium-dose group）， LVWI， the levels of CK， LDH， NT-proBNP， Col Ⅰ and Col Ⅲ in the myocardial tissue of rats were decreased significantly （P＜0.05）； the degree of myocardial fibrosis in rats decreased； protein and mRNA expressions of ADA and ADK in the myocardial tissue were significantly increased （P＜0.05）. CONCLUSIONS Arbutin can improve cardiac fibrosis and cardiac function of MF model rats， the mechanism of which may be associated with up-regulating protein and mRNA expressions of ADA and ADK，influencing the nucleotide metabolism and collagen generation. zhangminghao@hactcm.edu.cn
ABSTRACT
Objective To investigate the expressions of interleukin-33 (IL-33),soluble growth stimulation expressed gene 2 (sST2) and transforming growth factor β1 (TGF-β1) in the patients with systemic sclerosis (SSc) and their correlations.Methods Serum IL-33,sST2 and TGF-β1 levels from 25 SSc patients and 25 healthy controls were determined by an enzyme linked immunosorbent assay (ELISA).The expressions of IL-33 in the damaged skin tissue of SSc patients and normal skin tissue were detected with the immunohistochemical staining.Results Serum IL-33 and TGF-β1 levels in SSc patients were significantly higher than that in healthy controls (P ＜ 0.05),and serum IL-33 levels were positively correlated with TGF-β1 levels in SSc patients (P ＜ 0.05).Immunohistochemical staining results showed that the expression level of IL-33 in the damaged skin tissue of SSc patients were significantly higher than that in normal skin tissue (P ＜ 0.05).However,there was no significant difference in the expression level of sST2 between SSc patinets and healthy controls.Conclusion Serum IL-33 levels in SSc patients increase significantly,which is correlated with the expression of TGF-β1,indicating that IL-33 may play an important role in the process of inflammation and fibrosis of SSc via the regulation of TGF-β1.