Negative regulation of the hepatic fibrogenic response by suppressor of cytokine signaling 1

Suppressor of cytokine signaling 1 (SOCS1) is an indispensable regulator of IFNγ signaling and has been implicated in the regulation of liver fibrosis. However, it is not known whether SOCS1 mediates its anti-fibrotic functions in the liver directly, or via modulating IFNγ, which has been implicated in attenuating hepatic fibrosis. Additionally, it is possible that SOCS1 controls liver fibrosis by regulating hepatic stellate cells (HSC), a key player in fibrogenic response. While the activation pathways of HSCs have been well characterized, the regulatory mechanisms are not yet clear. The goals of this study were to dissociate IFNγ-dependent and SOCS1-mediated regulation of hepatic fibrogenic response, and to elucidate the regulatory functions of SOCS1 in HSC activation. Liver fibrosis was induced in Socs1^−/−Ifng^−/− mice with dimethylnitrosamine or carbon tetrachloride. Ifng^−/− and C57BL/6 mice served as controls. Following fibrogenic treatments, Socs1^−/−Ifng^−/− mice showed elevated serum ALT levels and increased liver fibrosis compared to Ifng^−/− mice. The latter group showed higher ALT levels and fibrosis than C57BL/6 controls. The livers of SOCS1-deficient mice showed bridging fibrosis, which was associated with increased accumulation of myofibroblasts and abundant collagen deposition. SOCS1-deficient livers showed increased expression of genes coding for smooth muscle actin, collagen, and enzymes involved in remodeling the extracellular matrix, namely matrix metalloproteinases and tissue inhibitor of metalloproteinases. Primary HSCs from SOCS1-deficient mice showed increased proliferation in response to growth factors such as HGF, EGF and PDGF, and the fibrotic livers of SOCS1-deficient mice showed increased expression of the Pdgfb gene. Taken together, these data indicate that SOCS1 controls liver fibrosis independently of IFNγ and that part of this regulation may occur via regulating HSC proliferation and limiting growth factor availability.     

Ultrastructural investigation of the protective effects of propolis on bleomycin induced pulmonary fibrosis

We investigated the antioxidant and anti-inflammatory effects of propolis on bleomycin induced lung fibrosis and compared these effects to prednisolone treatment. Forty rats were divided into four groups of ten: group 1 was treated with intratracheal infusion of 0.2 ml physiological saline followed by daily treatment with 0.5 ml physiological saline for 20 days. In the remaining groups (groups 2 ? 4), 5 mg/kg bleomycin was given via the trachea. Rats in group 2 were given 0.5 ml physiological saline. Rats in group 3 were treated with 100 mg/kg propolis, and 10 mg/kg prednisolone was given to rats in group 4. The treatments for all groups were continued for 20 days. On postoperative day 21, blood and lung samples were taken for biochemistry, histopathology and electron microscopy evaluation. We compared oxidative stress parameters and found lower malondialdehyde and myeloperoxidase levels, and higher total sulfhydryl levels and catalase activities for the bleomycin + propolis group than for the bleomycin and bleomycin + prednisolone groups. The highest mean fibrosis score was detected in the bleomycin group. Although the mean fibrosis scores of the bleomycin + propolis and bleomycin + prednisolone groups were not significantly different, electron microscopy revealed that propolis diminished bleomycin induced lung fibrosis more effectively than prednisolone. The effects of propolis might be due to its potent antioxidant and anti-inflammatory properties.     

急性冠脉综合征患者NLR、MPV与Gensini评分的相关性分析

目的:探讨急性冠脉综合征(Acute Coronary Syndrome,ACS)患者的中性粒细胞/淋巴细胞(Neutrophils/lymphocyte,NLR)、平均血小板体积(Mean platelet volume,MPV)与Gensini评分的相关性。方法:将156例ACS患者依据冠状动脉造影结果分为单支病变组、双支病变组及三支病变组,比较各组间NLR、MPV、Gensini评分及一般临床资料,并分析不同指标之间的相关性。结果:与双支病变组、单支病变组相比较,三支病变组吸烟、糖尿病、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、尿酸(uric acid,UA)、NLR、MPV、Gensini评分均显著升高(P0.05);与单支病变组相比较,双支病变组吸烟、糖尿病、LDL-C、HDL-C、UA、NLR、MPV、Gensini评分均显著升高(P0.05);三组间年龄、性别、高血压、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、肌酐(creatinine,Cr)比较差异均无统计学意义(P0.05)。Pearson相关性分析表明:NLR、MPV与Gensini评分均呈正相关(r=0.482、0.702, P0.05)。结论:ACS患者MPV和NLR与冠状动脉病变程度呈显著正相关,可有效评估冠状动脉狭窄程度。     

老年冠心病患者血清Lp-PLA2、hs-CRP、IL-27及MMP-9水平与Gensini积分的相关性研究*

目的:探讨老年冠心病患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)、高敏C反应蛋白(hs-CRP)、白细胞介素-27(IL-27)及基质金属蛋白酶-9(MMP-9)水平与Gensini积分的相关性。方法:选取2015年10月至2018年2月我院收治的冠心病患者142例为研究对象,将所有患者按照不同的冠心病类型分为不稳定型心绞痛(UAP)组54例、稳定型心绞痛(SAP)组40例和急性心肌梗死(AMI)组48例。同时根据患者Gensini积分将其分为轻度47例、中度51例和重度44例。比较不同冠心病类型、不同严重程度的Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分,并分析冠心病患者上述指标水平与Gensini积分的相关性。结果:AMI组患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分均高于UAP组和SAP组,且UAP组高于SAP组(P0.05)。重度患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分均高于中度和轻度患者,且中度患者高于轻度患者(P0.05)。经Spearman相关性分析结果显示,冠心病患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平与Gensini积分均呈正相关(P0.05)。结论:老年冠心病患者Lp-PLA2、hs-CRP、IL-27及MMP-9水平与患者冠状动脉病变Gensini积分均呈正相关。临床根据Lp-PLA2、hs-CRP、IL-27及MMP-9水平的变化,有助于评估老年冠心病患者的病情严重程度。     

肺脏超声对新生儿呼吸窘迫综合征的诊断价值及肺超声评分的评估价值分析

目的:探讨肺脏超声对新生儿呼吸窘迫综合征(NRDS)的诊断价值,并分析肺超声评分的临床应用价值。方法:本研究选择2017年5月至2018年5月于我院确诊的NRDS患儿45例作为观察组,选择同期于我院就诊的非肺病患儿45例作为对照组,所有患儿均行肺脏超声检查。分析NRDS患儿肺脏超声特征性征象,比较肺脏超声对两组患儿各种征象的检出率,分析肺脏超声对NRDS的诊断价值,比较两组肺超声评分。结果:NRDS患儿全部存在肺实质征象,超声下肺组织回声呈肝样伴支气管充气征,轻度的NRDS患儿于肺脏超声下表现为局灶性的肺实质,且支气管充气征不明显;重度的NRDS患儿于肺脏超声下表现为肺实质范围的进一步扩大,且支气管充气征随病情的加重而愈发明显。观察组肺实质、胸膜线异常、A线消失、弥漫性肺水肿、支气管充气征等征象的检出率显著高于对照组(P0.05),两组B线存在征象的检出率比较无统计学差异(P0.05)。肺实质、胸膜线异常和A线消失三种特征征象同时存在时对NRDS诊断的灵敏度和特异性均为100.00%,肺实质、胸膜线异常和支气管充气征三种特征征象同时存在时对NRDS诊断的灵敏度为80.00%,特异性为100.00%。观察组双肺、左肺、右肺、双侧肺、双肺底肺超声评分均高于对照组(P0.05)。结论:肺脏超声对NRDS的诊断价值较高,且肺超声评分可以评估NRDS患儿的病情严重程度,有助于指导患儿的治疗。     

血府逐瘀汤联合四联疗法治疗Hp阳性慢性萎缩性胃炎的临床观察

目的:探究血府逐瘀汤联合四联疗法治疗幽门螺旋杆菌(Hp)阳性慢性萎缩性胃炎的效果。方法:回顾性分析2014年5月-2017年12月在我院进行诊治的80例Hp阳性慢性萎缩性胃炎患者的临床资料,按照其入院顺序经随机数字表分为研究组和对照组,每组各40例患者。其中,对照组患者采用四联疗法,研究组患者在对照组基础上联合血府逐瘀汤进行治疗,对比两组患者的Hp转阴率、治疗前后胃黏膜病理积分的变化情况、临床症状积分的变化情况和不良反应发生率。结果:治疗后,研究组患者的Hp转阴率[85.0%(34/40)]显著高于对照组[62.5%(25/40)](P0.05)。两组上腹痛、纳差、上腹胀、反酸、嗳气等临床症状积分以及胃黏膜萎缩、肠化、不典型增生等病理积分均显著低于治疗前(P0.05),且研究组以上指标均明显低于对照组(P0.05)。研究组患者的不良反应发生率[5.0%(2/40)]与对照组[12.5%(5/40)]无显著性差异(P0.05)。结论:血府逐瘀汤联合四联疗法治疗Hp阳性慢性萎缩性胃炎的效果显著优于单用四联疗法,其可有效改善患者的病变程度和临床症状,且无明显不良反应产生。     

心肌纤维化的信号转导机制及新型抑制剂的研究进展

心肌纤维化(myocardial fibrosis, MF)是心肌重构发生的重要病理过程,能够引起心脏衰竭甚至死亡。心肌组织中成纤维细胞异常增殖并转化为肌成纤维细胞以及心肌细胞外基质代谢紊乱导致沉积是心肌纤维化形成的主要病理基础。心肌纤维化发生的分子机制较复杂,已发现多种信号通路参与了心肌纤维化的发生。该文主要对参与调控心肌纤维化的信号转导机制进行了综述,并对新型信号抑制剂的研究进展进行了小结。     

Danqi soft capsule prevents infarct border zone remodelling and reduces susceptibility to ventricular arrhythmias in post‐myocardial infarction rats

Danqi soft capsule (DQ) is a traditional Chinese medicine containing Salvia miltiorrhiza and Panax notoginseng; it is safe and efficient in treating ischaemic heart diseases. The purpose of the present study was to assess whether DQ could prevent infarct border zone (IBZ) remodelling and decrease ventricular arrhythmias occurrence in post‐myocardial infarction (MI) stage. MI was induced by a ligation of the left anterior descending coronary artery. DQ was administered to the post‐MI rats started from 1 week after MI surgery for 4 weeks. The results showed that DQ treatment significantly attenuated tachyarrhythmia induction rates and arrhythmia score in post‐MI rats. In echocardiography, DQ improved left ventricular (LV) systolic and diastolic function. Histological assessment revealed that DQ significantly reduced fibrotic areas and myocyte areas, and increased connexin (Cx) 43 positive areas in IBZ. Western blot revealed that DQ treatment significantly reduced the protein expression levels of type I and III collagens, α‐smooth muscle actin (α‐SMA), transforming growth factor‐β1 (TGF‐β1) and Smad3 phosphorylation, while increasing Cx43 amounts. Overall, these findings mainly indicated that DQ intervention regulates interstitial fibrosis, Cx43 expression and myocyte hypertrophy by TGF‐β1/Smad3 pathway in IBZ, inhibits LV remodelling and reduces vulnerability to tachyarrhythmias after MI. This study presents a proof of concept for novel antiarrhythmic strategies in preventing IBZ remodelling, modifying the healed arrhythmogenic substrate and thus reducing susceptibility to ventricular arrhythmias in the late post‐MI period.     

rSJYB1 inhibits collagen type I protein expression in hepatic stellate cells via down‐regulating activity of collagen α1 (I) promoter

YB1 is a negative regulator in liver fibrosis. We wondered whether SJYB1, a homologous protein of YB1 from Schistosoma japonicum, has an effect on liver fibrosis in vitro. Recombinant SJYB1 (rSJYB1) protein was expressed in a bacterial system and purified by Ni‐NTA His·Bind Resin. A human hepatic stellate cell line, the LX‐2 cell line, was cultured and treated with rSJYB1. The role of rSJYB1 on LX‐2 cells was then analysed by Western blot and luciferase assay. We succeeded in expressing and purifying SJYB1 in a bacterial system and the purified rSJYB1 could be recognized by S japonicum‐infected rabbit sera. Western bolt analysis showed that rSJYB1 inhibited the expression of collagen type I, but had little effect on α‐smooth muscle actin (α‐SMA). Further analysis revealed that rSJYB1 inhibited the activity of collagen α1 (I) (COL1A1) promoter and functioned at ?1592/?1176 region of COL1A1 promoter. Our data demonstrate that rSJYB1‐mediated anti‐fibrotic activity involves inhibiting the activity of COL1A1 promoter and subsequently suppressing the expression of collagen type I in hepatic stellate cells.