中药射干亲脂中性成分研究

射干(Belamcanda chinensis(L.)DC)根茎是常用中药。主治咽喉肿痛。Mannich报道含有鸢尾甙(tectoridin)。九谷 昇证明含有野鸢尾甙(iridin),Woo将射干粗提取物作纸层析报道可见生物碱反应色点,未见进一步工作。 本文从射干根茎的亲脂中性部分分离获得三个单体:     

A-FABP and Oxidative Stress Underlie the Impairment of Endothelium-Dependent Relaxations to Serotonin and the Intima-Medial Thickening in the Porcine Coronary Artery with Regenerated Endothelium

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Mechanism of p47phox-induced increase of reactive oxygen species in peripheral blood mononuclear cells from premature infants on oxygen therapy

Objective: This study aimed to explore the mechanism of p47phox-induced increase of reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) from premature infants after oxygen therapy, and determine a new target for oxidative stress injury alleviation in clinical setting.

Methods: First, ROS levels as well as p47phox translocation and expression in PBMC samples were evaluated after treatment of premature infants with different concentrations of oxygen. Then, changes of all various parameters were detected after in vitro treatment of PBMCs with diphenyleneiodonium (DPI), apocynin, and high oxygen levels.

Results: In premature infants, ROS levels increased significantly after treatment with oxygen, in a concentration-dependent manner (p?<?0.05); meanwhile, p47phox translocation and expression were significantly enhanced (p?<?0.05) as well. In agreement, PBMCs cultured in vitro showed increased ROS levels after treatment with high oxygen concentrations; p47phox translocation, and expression increased as well (p?<?0.05). However, treatment with DPI or apocynin resulted in opposite effects.

Conclusion: Treatment with oxygen increases p47phox translocationand expression, which in turn induce ROS production. DPI and apocynin have the opposite effects.     

Apocynin combined with drugs as coadjuvant could be employed to prevent and/or treat the chronic kidney disease

A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO^? to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH₄), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion (). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress () and endothelial function (BH4). There were significantly lower levels of and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.     

夹竹桃麻素对高草酸尿症大鼠肾脏氧化应激损伤的保护作用

目的 观察NADPH氧化酶特异抑制剂夹竹桃麻素（apocynin）对高草酸尿症大鼠肾脏氧化应激（OS）损伤的保护作用。 方法 自由饮用含有0.8%乙二醇的水4周建立高草酸尿症SD大鼠模型。大鼠按随机数字表法分为4个组：空白组、高草酸尿症组、apocynin干预组、apocynin对照组。后两组给予apocynin（0.2 g&#8226;kg-1&#8226;d-1）灌胃,对照组给予正常饮水。4周后检测大鼠肾脏OS 指标（尿H2O2和8-异前列腺素）,以及Ccr及肾脏/体质量比值。免疫组化观察NADPH氧化酶亚基p47phox在肾脏中的表达位置。RT-PCR和免疫印迹法分别检测肾组织NADPH氧化酶亚基p47phox、gp91phox、Nox-1 mRNA以及p47phox蛋白的表达水平。 结果 p47phox在各组肾脏中均有广泛的表达,包括肾皮质区、内髓区、外髓区等。与空白组比较,高草酸尿症组大鼠尿H2O2和8-异前列腺素水平显著升高,Ccr降低,肾脏/体质量比值增高（均P < 0.05）;肾脏p47phox、gp91phox和Nox-1 的mRNA表达均显著增加（均P ＜ 0.05）, p47phox蛋白表达也增多（P ＜ 0.01）。apocynin干预治疗可抑制肾脏p47phox、Nox-1 mRNA及p47phox蛋白的表达,但gp91phox mRNA表达未明显减少,而大鼠尿H2O2和8-异前列腺素水平下降,Ccr增加,肾脏/体质量比值减少,但仍高于对照组水平。 结论 NADPH氧化酶是高草酸尿症诱导大鼠肾脏OS损伤过程中活性氧形成的来源之一。使用apocynin抑制NADPH氧化酶活性可部分减轻肾脏的OS损伤程度,保护肾功能。     

血管紧张素Ⅱ刺激高草酸尿症大鼠肾脏NADPH氧化酶的表达

目的： 观察肾素-血管紧张素系统（RAS）和NADPH氧化酶在高草酸尿症大鼠肾脏氧化应激（OS）形成中的相互作用。方法: 采用0.8%乙二醇饮水法诱导建立高草酸尿症大鼠模型。动物分6个组（n=8）,A组:空白组;B组：高草酸尿症组;C组：高草酸尿症+apocynin治疗组;D组：单纯apocynin治疗组;E组：高草酸尿症+losartan治疗组;F组：单纯losartan治疗组。后4组分别灌胃给予apocynin（0.2 g·kg-1·d-1）或losartan（30 mg·kg-1·d-1）。4周后检测大鼠尿液、肾组织中的OS指标（尿8-IP和肾组织SOD活性）,放免法检测肾组织血管紧张素Ⅱ（AngⅡ）的含量,免疫组化法观察NADPH氧化酶亚单位P47phox蛋白在肾脏中的表达位置,RT-PCR法检测肾组织p47phox mRNA的表达水平。结果: p47phox在各组大鼠肾脏中都有广泛表达,表达部位包括肾皮质、内髓、外髓。与A组比较,B组尿液8-IP明显增多,肾组织SOD活性降低,肾组织AngⅡ含量增多,p47phox mRNA在肾组织中的表达水平也明显增多。使用apocynin（C组）和losartan（E组）均可抑制肾组织p47phox mRNA的表达,同时肾脏的OS程度减轻。结论: 在高草酸尿症大鼠模型中,肾脏p47phox mRNA表达增多,导致肾脏OS;同时肾脏RAS也被激活,后者可通过刺激p47phox mRNA的表达而促进肾脏OS程度增加。     

Protective effects of apocynin and allopurinol on ischemia/reperfusion-induced liver injury in mice

AIM： To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion （I/R） procedure in mice.
METHODS： Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase （NOX） inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion.
RESULTS： A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure.
CONCLUSION： Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.     

Apocynin对缺血再灌注后急性肾损伤的保护作用

目的 观察Apocynin对急性缺血再灌注肾损伤（I/R）大鼠模型的保护作用并探讨其机制.方法 采用雄性SD大鼠制备急性缺血再灌注肾损伤模型,用不同浓度（5 mg/kg、10 mg/kg、20 mg/kg） Apocynin干预,同时设定假手术组、手术对照组,生化法测定血肌酐值,光镜下观察肾组织形态学变化并进行肾小管病变计分,免疫组织化学检测肾组织单核巨噬细胞计数,硫代巴比妥酸比色法测定肾组织匀浆丙二醛（MDA）,改良DTNB显色法测定血清谷胱甘肽过氧化物酶（GPx）,ELISA法测定血清白介素1（IL-1）.结果 与假手术组相比,手术对照组血肌酐明显升高（P＜0.05）,肾小管计分明显升高（P＜0.05）,肾组织巨噬细胞数目增加（P＜0.05）,血清MDA、IL-1升高（P＜0.05）,GPx下降（P＜0.05）;与手术对照组相比,各Apocynin干预组血肌酐下降（P＜0.05）,肾小管计分降低（P＜0.05）,肾组织巨噬细胞数目减少（P＜0.05）,血清MDA降低（P＜0.05）,IL-1降低（P＜0.05）,GPx含量升高（P＜0.05）.结论 Apocynin可以降低急性缺血再灌注肾组织氧化应激水平,抑制炎症反应,减轻肾功能损伤程度.     

Reducing age-dependent monocyte-derived macrophage activation contributes to the therapeutic efficacy of NADPH oxidase inhibition in spinal cord injury

ObjectiveThe average age at the time of spinal cord injury (SCI) has increased to 43 years old. Middle-aged mice (14 months old, MO) exhibit impaired recovery after SCI with age-dependent increases in reactive oxygen species (ROS) production through NADPH oxidase (NOX) along with pro-inflammatory macrophage activation. Despite these aging differences, clinical therapies are being examined in individuals regardless of age based upon preclinical data generated primarily using young animals (∼4 MO). Our objective is to test the extent to which age affects SCI treatment efficacy. Specifically, we hypothesize that the effectiveness of apocynin, a NOX inhibitor, is age-dependent in SCI.MethodsApocynin treatment (5 mg/kg) or vehicle was administered 1 and 6 h after moderate T9 contusion SCI (50kdyn IH) and then daily for 1 week to 4 and 14 MO mice. Locomotor and anatomical recovery was evaluated for 28 days. Monocyte-derived macrophage (MDM) and microglial activation and ROS production were evaluated at 3 and 28 days post-injury.ResultsApocynin improved functional and anatomical recovery in 14 but not 4 MO SCI mice. Apocynin-mediated recovery was coincident with significant reductions in MDM infiltration and MDM-ROS production in 14 MO SCI mice. Importantly, microglial activation was unaffected by treatment.ConclusionThese results indicate that apocynin exhibits age-dependent neuroprotective effects by blocking excessive neuroinflammation through NOX-mediated ROS production in MDMs. Further, these data identify age as a critical regulator for SCI treatment efficacy and indicate that pharmacologically reduced macrophage, but not microglia, activation and ROS production reverses age-associated neurological impairments.     

NADPH氧化酶下调海马内微清蛋白表达在老年小鼠术后认知功能障碍中的作用

目的观察海马内微清蛋白(PV)表达变化在老年小鼠术后认知功能障碍(POCD)中的作用,并探讨磷酸酰胺腺嘌呤二核苷酸(NADPH)氧化酶是否参与其中。方法采用异氟醚麻醉+剖腹探查术建立POCD动物模型。雄性16月龄C57BL/6小鼠21只,随机均分为三组(n=7):对照+溶剂组(C+V组)、异氟醚麻醉+剖腹探查+溶剂组(POCD+V组)、异氟醚麻醉+剖腹探查+夹竹桃麻素组(POCD+A组)。POCD+A组术后1h腹腔注射夹竹桃麻素5mg/kg,其后每天注射一次直至术后第7天;其余两组注射等容量的溶剂。术后第6天行旷场实验和条件性恐惧实验训练,第7天在给予药物或溶剂后2h行条件性恐惧测试。行为学测试后2h取小鼠海马组织,采用Western blot检测PV、gp91phox、p22phox及羟基壬烯酸(4-HNE)的表达变化。结果三组小鼠总探索路程和中央格停留时间差异无统计学意义。与C+V组比较,POCD+V组在场景性条件恐惧测试中僵直时间明显缩短,海马PV表达明显下降,而gp91phox、p22phox和4-HNE表达明显升高(P0.05);与POCD+V组比较,POCD+A组在场景性条件恐惧测试中僵直时间明显延长,海马PV表达明显升高,gp91phox、p22phox和4-HNE表达明显降低(P0.05)。结论海马NADPH氧化酶活化介导PV表达降低可能参与老年小鼠POCD。