脂氧素 A4预处理对糖尿病大鼠心肌缺血再灌注时Caspase －3、Bcl －2和 Bax 表达的影响

目的：观察脂氧素 A4预处理对链尿佐菌素诱导的糖尿病大鼠心肌缺血再灌注时 Caspase －3、Bcl －2和 Bax 表达的影响。方法雄性 SD 大鼠60只,随机分为 CS、CI／R、CLX、DS、DI／R、DLX 组共6组（n ＝10）。 CS、CI／R、CLX组采用腹腔注射链尿佐菌素55 mg／kg 制备糖尿病模型。 CI／R、DI／R组建立大鼠心肌缺血再灌注模型,结扎冠脉左前降支30 min,CS 组和 DS 组仅穿线不结扎,CI／R组和 DI／R组缺血前5 min 经股静脉注射2 mL／kg 生理盐水,CLX组和 DLX组缺血前5 min 经股静脉注射脂氧素 A42.5μg／kg。再灌注4 h 时处死大鼠,取心肌组织,采用 HE 染色法光镜下观察缺血心肌组织形态学改变,通过 RT －PCR 和 Western blot 法检测缺血心肌 Caspase －3、Bcl －2和 Bax的表达水平,并计算 Bcl －2与 Bax 表达的比值（Bcl －2／Bax）。结果CLX组和 DLX组心肌组织病理学损伤较 CI／R组和 DI／R组减轻,Caspase －3和 Bax 的表达量减少,Bcl －2的表达量增加,Bcl －2／Bax 比值升高（P ＜0.05）。结论脂氧素 A4预处理能够下调糖尿病大鼠心肌缺血再灌注时 Caspase －3和 Bax 的表达,上调 Bcl －2的表达,使 Bcl －2／Bax 比值升高。     

KSHV genotypes A and C are more frequent in Kaposi sarcoma lesions from Brazilian patients with and without HIV infection, respectively

Macrophages play an important role in tumor inflammatory microenvironment, lipoxin (LX), the 'stop signal' for inflammation, has been extensively studied preclinically for its anti-inflammatory or inflammatory pro-resolving effect. Here, we showed that LXA(4) could promote the apoptosis and inhibit the proliferation, migration and angiogenesis of HepG2 hepatocarcinoma cells stimulated by lipopolysaccharide (LPS) or activated macrophage-conditioned media (ACM). Moreover, BML-111, the analog of LXA(4), effectively inhibited the proliferation, invasion and angiogenesis of tumor in H22 hepatocarcinoma cell bearing mice. These results showed that LXA(4) could be a possible candidate for liver cancer therapy, and blocking the activation of macrophages would be an effective drug target.     

护场理论指导下的箍围法对皮肤脓肿大鼠血浆高迁移率族蛋白1、脂氧素A4表达的影响

目的观察护场理论指导下的箍围法(红肿消)对皮肤脓肿大鼠血浆内高迁移率族蛋白1(HMGB1)、脂氧素A4(LXA4)表达的影响。方法 40只大鼠,随机分为空白组、模型组、对照组、预治疗组、治疗组。除空白组外,其余4组皮下注射金黄色葡萄球菌1 mL(3~5×10~9CFU/mL)造成皮下脓肿模型。模型组生理盐水换药,对照组莫匹罗星软膏外涂换药,预治疗组在注射细菌后4h用红肿消2 mL换药,治疗组用红肿消2 mL换药,药物范围超过肿胀范围1 cm,换药每日1次。分别于治疗3、7、14、18 d心脏取血2 mL,ELISA法检测血浆内HMGB1、LXA4的表达。结果治疗3 d时,与空白组比较模型组HMGB1含量较低(P0.01);与模型组比较预治疗组、治疗组HMGB1含量较高(P0.01或P0.05)。治疗3 d,与空白组比较,模型组、对照组、治疗组LXA4含量升高(P0.01或P0.05);与模型组比较,预治疗组LXA4含量较低(P0.01)。治疗18 d,对照组与空白组和模型组比较LXA4含量升高(P0.05)。结论早期应用箍围法(红肿消)可提高大鼠血浆内LXA4的表达,主要参与早期炎症抑制作用,同时可能通过缩短炎症反应进程、在治疗早期提前促使HMGB1的释放并抑制中后期HMGB1的释放和(或)阻止HMGB1的促炎活性,从而有效促进护场形成。     

Mediators and receptors in the resolution of inflammation: drug targeting opportunities

The active resolution of inflammation is recognized as offering new opportunities to generate novel anti-inflammatory agents. The emerging appreciation of the importance of active resolution in regulation of inflammation also creates an imperative to examine developing and existing agents for their potential to influence these pathways. This themed issue of the British Journal of Pharmacology contains papers that discuss the roles of annexin-1, lipoxins and related lipid products of fish oils as well as other mechanisms involved in active resolution and their receptor targets.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

脂氧素A4调节Smad7／3表达对糖尿病肾脏保护机制实验研究

目的观察脂氧素A4对链脲佐菌素诱导的实验性糖尿病大鼠肾脏Smad7／Smad3表达调节,探讨其对糖尿病大鼠肾脏保护作用及机制。方法选择年龄3月左右、体质量212～245g清洁级健康雄性sD大鼠,以60mg／kg体质量链脲左菌素诱导糖尿病大鼠模型,选择制模成功的糖尿病模型大鼠20只,分为脂氧素A4给药组（E组,n=10）、生理盐水对照组（c组,n=10）。E组以1ms／kg体质麓脂氧素A4,c组则以相应剂量生理盐水尾静脉注射,隔日1次,连续4周,取大鼠肾脏标本,采用免疫组织化学法观察肾脏Smad7、Smad3以及转换生长因子8l表达。结果E组与C组Smad7、Smad3以及转换生长因子B1阳性表达面积百分率对数（In）分别为（3．15±0．04）％与（2．96±0．03）％、（2．58％±0．05）％与（2．88±0．05）％和（2．98±0．05）％与（3．16±0．04）％,E组Smad7阳性表达面积百分率明显高于c组,而Smad3以及转换生长因子8l则明显低于c组,差异均有统计学意义（P〈0．01、0．01、0．05）。结论脂氧素A4能上调糖尿病大鼠肾脏Smad7、下调Smad3及转换生长因子Bl表达,对糖尿病大鼠肾脏具有保护作用。