目的 观察紧密连接蛋白在高尿酸血症致大鼠肾损害模型中的表达变化以及非布司他的干预疗效。方法 将SD大鼠分为正常组,高尿酸血症组(模型组),非布司他组(干预组);氧嗪酸联合尿酸诱导制作高尿酸血症大鼠模型,给予非布司他进行干预,分别于6周后检测各组大鼠血中尿素氮(BUN)、血肌酐(Scr)、尿酸(UA)水平,免疫组化及RT-PCR方法检测紧密连接蛋白包括膜周蛋白-1(ZO-1)、跨膜蛋白(occludin) 的表达变化,采用Masson染色检测大鼠肾间质病理改变。结果 6周时,模型组、干预组ZO-1、occludin表达较正常组降低(均P<0.05);干预组ZO-1、occludin表达较模型组增加,差异有统计学意义(均P<0.05),与正常组相比,模型组、干预组RIF指数均增高(均P<0.05),干预组RIF指数低于模型组,高于正常组(均P<0.05)。结论 紧密连接蛋白表达的降低在高尿酸血症肾间质纤维化发展过程中起着举足轻重的作用,并与血尿酸水平及肾功能损害密切相关。非布司他通过降低血尿酸水平,能改善紧密连接蛋白的表达,延缓肾功能损害,起到肾保护作用。

Objective To observe the expression of tight junction protein in hyperuricemia induced renal damage model in rats and the intervention effect of febuxostat. Methods SD rats were randomly divided into three groups: normal control group, model control group, febuxostat treatment group. Hyperuricemia was induced in rats with oxonic acid per time for three times per day, by gavage and combined with uric acid added in drinking water, while febuxostat were administered by gavage in febuxostat treatment group.The blood of rats were collected to analyse the differences of control, model and treatment group on changes of blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA). Immunohistochemistry was used to assay ZO-1 and occludin protein expression and quantitive real time PCR to detect the expression of ZO-1 and occludin in renal tissue of renal interstitial fibrosis model rats induced by hyperuricemia. Paraffin section of kidney was maked and then performed Masson staining to make sure the model is successful. Results At 6 weeks, the expressions of ZO-1 and occludin in the model group and treatment group were lower than those in the normal group (all P<0.05). The expressions of ZO-1 and occludin in the treatment group were higher than those in the model group (all P<0.05). Compared with the normal group, the RIF index in the model group and treatment group were higher (all P<0.05), and the RIF index in the treatment group was lower than that in the model group and higher than that in the normal group (all P<0.05). Conclusion The downregulated expression of ZO-1 and occludin plays a crucial role during the development of hyperuricemia in renal interstitial fibrosis, and are closely related to UA level and renal function impairment. Febuxostat may improve the expression of tight junction by downregurating UA, reduce renal fuction impairment and play a role in renal protection.

目的 探讨特发性肺纤维化(IPF)患者和结缔组织病相关性纤维化间质性肺疾病(CTD-fILD)患者急性加重(AE)的短期内死亡的危险因素。方法 回顾性分析2017年10月—2019年9月在深圳大学和广州医科大学附属第一医院住院的25例 AE-CTD-fILD和26例AE-IPF患者临床信息,Kaplan-Merier法对两组患者进行生存分析,Cox回顾分析年龄、性别、吸烟、白细胞总数、C反应蛋白、红细胞沉降率及肿瘤指标在急性加重患者死亡中的作用。结果 与AE-CTD-fILD比较,AE-IPF患者组男性比例、年龄、吸烟比例较高,红细胞沉降率较低(24/26 vs 10/25,P<0.001;63.77±9.97 vs 58.00±10.32,P=0.048;16/26 vs 9/25,P=0.02;28.07±29.45 vs 64.35±40.34,P=0.002 );90天内,26例AE-IPF患者11例死亡,25例AE-CTD-fILD患者5例死亡,死亡率无明显差异(42.3% vs 20%,P=0.073);Cox回归分析显示,白细胞计数是AE-IPF和AE-CTD-fILD患者的死亡危险因素(HR=1.305,P=0.001;HR=1.529,P=0.009);CA15-3是AE-IPF患者死亡危险因素(HR=1.015,P=0.005)。结论 急性加重IPF和CTD-fILD患者短期内死亡风险相似,白细胞计数及外周CA15-3水平可能是肺纤维化急性加重患者短期内死亡的危险因素。

Objective To explore the risk factors for acute exacerbation (AE) in patients with idiopathic pulmonary fibrosis (IPF) and connective tissue disease associated with fibrotic interstitial lung disease (CTD-fILD). Methods We retrospectively reviewed 25 patients with AE-CTD-fILD and 26 patients with AE-IPF, and Kaplan-Merier was used to analyze the survival of the two groups of patients. The impact of age,gender, smoking,WBC,CRP,ESR and tumor markers on acute exacerbation death were performed by Cox regression analysis. Results The AE-IPF patients had a higher proportion of men,age and smoking,and a lower ESR compared with AE-CTD-fILD patients(24/26 vs 10/25,P<0.001;63.77±9.97 vs 58.00±10.32,P=0.048;16/26 vs 9/25,P=0.02;28.07±29.45 vs 64.35±40.34,P=0.002 ). 11 cases of 26 patients with AE-IPF and 5 cases of 25 patients with AE-CTD-fILD died within 90 days, Log-rank tests showed patients with CTD-fILD had similar mortality rate compared with IPF patients after AE(42.3% vs 20%,P=0.073). The WBC count was negatively correlated with survival and the independent predictors for patients with AE-IPF and AE-CTD-fILD after adjusting for other clinical variates in Cox regression models(HR=1.305,P=0.001;HR=1.529,P=0.009). CA15-3 may be a risk factor for death of AE-IPF patients(HR=1.015,P=0.005). Conclusion AE-CTD-fILD and AE-IPF were associated with similar poor short-term survival, WBC count and plasma CA15-3 may be the independent survival predictors respectively for patients with acute exacerbation of pulmonary fibrosis in short term.

目的 探讨雷公藤甲素防治大鼠青光眼术后滤过泡纤维化的可行性。方法 选取Wistar大鼠100只分为两组,对照组和观察组各50例。采用房水释放联合激光房角光凝法建立青光眼大鼠模型,然后所有大鼠均进行青光眼手术。手术后,观察组大鼠使用雷公藤甲素预防治疗青光眼术后滤过泡纤维化,对照组大鼠使用5-氟尿嘧啶预防治疗青光眼术后滤过泡纤维化。观察比较防治滤过泡纤维化效果。结果 观察组大鼠的眼压在手术后第1天与对照组相比无差异(P＞0.05),在第6天、14天低于对照组(P＜0.05),观察组大鼠滤过泡面积在手术后第1天、6天、14天均小于对照组大鼠(P＜0.05);观察组大鼠的治疗后滤过泡分型Ⅰ型和Ⅱ型均优于对照组,Ⅲ型和Ⅳ型均低于对照组(P＜0.05);观察组术后不良反应发生率为12.16%,低于对照组22.86%(P＞0.05)。结论 雷公藤甲素防治大鼠青光眼术后滤过泡纤维化效果明显,且安全性较高,值得临床广泛运用推广。

Objective To investigate the feasibility of triptolide in prevention and cure rats glaucoma surgery fibrosis. Methods 100 cases of Wistar rats were divided into two groups, with 50 cases in the control group and the observation group.Glaucoma rat model were built by aqueous release combined with laser photocoagulation, and all rats underwent glaucoma surgery. After surgery, the rats in the observation group were observed their triptolide preventive treatment in glaucoma surgery fibrosis, the control rats were observed their 5-fluorouracil preventive treatment in glaucoma surgery fibrosis.The effects of prevention and treatment of bleb fibrosis were compared. Results The intraocular pressure of rats in observation group in the first day after surgery compared with the control group has no significant difference (P>0.05), on the 6th、 14th day it was lower than the control group rats(P<0.05). Filtration area in the observation group on first, 6th day, 14th days after surgery, was less than the control rats(P<0.05); In the observation group, the type Ⅰ and type Ⅱ of filtering bleb were better than those of the control group, the type Ⅲ and type Ⅳ were lower than those of the control group (P<0.05);The adverse reaction rate was 12.16% in observation group, it was lower than the control group 22.86% (P<0.05). Conclusion Triptolide in prevention and cure of rats glaucoma surgery fibrosis is obvious, and high security. It is worthy of promotion.