Imaging agents for myeloperoxidase

The myeloperoxidase (MPO) inhibitors 1 and 2 were prepared as their isotopologues with carbon‐14, carbon‐13, and nitrogen‐15 or tritium with high specific activity and purity. Starting from potassium [¹⁴C]cyanide or [¹⁴C]formate provided metabolically stable ¹⁴C‐labels on [¹⁴C]‐1 and [¹⁴C]‐2. Catalytic hydrogenation was used for the preparation of [³H]‐2, giving multiple enriched positions as shown by ³H NMR. 1 and 2 are promising in vitro and in vivo imaging radioligands and have the potential to provide key information with regard to MPO expression, function, stoichiometry, and pharmacology.     

Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats

Oxidative stress, neutrophil infiltration, proinflammatory cytokines and eicosanoid generation are clearly involved in the pathogenesis of intestinal bowel disease. Resveratrol, a polyphenolic compound found in grapes and wine, has been shown to have anti-inflammatory, antioxidant, antitumour and immunomodulatory activities, however, its effects on experimental colitis remain unknown. We have investigated the effects of resveratrol on the colon injury caused by intracolonic instillation of trinitrobenzenesulphonic acid (TNBS) in rats. We determined the production of prostaglandin (PG)E(2) and PGD(2) in colon mucosa and the expression of cyclo-oxygenases (COX)-1 and -2 immunohistochemically. The inflammatory response was assessed by histology and myeloperoxidase activity, as an index of neutrophil infiltration. Interleukin-1 beta production, histological and histochemical analysis of the lesions were also carried out. Finally, since resveratrol has been found to modulate apoptosis we intended to elucidate its effects on colonic mucosa under early acute inflammatory conditions. Resveratrol (5-10mg/kg/day) significantly reduced the degree of colonic injury, the index of neutrophil infiltration and the levels of the cytokine. Resveratrol did not revert the increased PGE(2) levels but produced a significant fall in the PGD(2) concentration. Compared with inflamed colon, no changes in staining for COX-1 were observed in colon of resveratrol and TNBS-treated rats. In contrast, COX-2 expression was decreased. Furthermore, resveratrol enhanced apoptosis compared with already high level induced by TNBS. In conclusion, resveratrol reduces the damage in experimentally induced colitis, alleviates the oxidative events and stimulates apoptosis.     

硫化氢对大鼠机体重要脏器的损伤观察

目的分析硫化氢（H2S）对正常大鼠机体重要脏器组织结构的损伤性作用及意义。方法 32只Wistar大鼠随机分为4组,即对照组、硫氢化钠（NaHS）2.8μmol/kg组、NaHS 8.4μmol/kg组和NaHS 14.0μmol/kg组。生物机能试验系统监测大鼠左室血流动力学性能,用亚甲蓝分光光度法测定血浆硫磺化氢（H2S）浓度,用ELISA法测定血浆肿瘤坏死因子（TNF-α）、髓过氧化物酶（MPO）浓度;HE染色观察大鼠心、肺、肝、肾和脑等脏器的组织结构改变。结果超生理浓度的H2S对健康大鼠左室血流动力学性能无明显影响（P〉0.05）,但静脉注射不同剂量NaHS后,大鼠血浆中肿瘤坏死因子-α（TNF-α）和髓过氧化物酶（MPO）浓度随血浆H2S浓度的增加而增加,尤其是NaHS14.0μmol/kg组血浆TNF-α和MPO浓度的增加较明显（P〈0.05）。结论超生理剂量H2S对健康大鼠左室流体动力学性能无影响,但可导致重要脏器的炎症反应。     

Evidence of anti-inflammatory effects of Passiflora edulis in an inflammation model

The popular medicine Passiflora edulis has been used as a sedative, tranquilizer, against cutaneous inflammatory diseases and intermittent fever. Most of the pharmacological investigations of Passiflora edulis have been addressed to its Central Nervous System activities, such as anxiolytic, anticonvulsant and sedative actions. Otherwise, there are few reports about the anti-inflammatory activity of the Passiflora species. The aim of this study was to investigate the mechanism of the anti-inflammatory effect of aqueous lyophilized extract obtained from leaves of Passiflora edulis var. flavicarpa Degener (Passifloraceae) in the mouse model of pleurisy induced by carrageenan (Cg), bradykinin, histamine or substance P, observing the effects upon leucocytes migration, myeloperoxidase (MPO), nitric oxide (NO) concentrations and tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1beta) levels. RESULTS: Passiflora edulis (250mg/kg) administered by intraperitoneal route (i.p.) inhibited the leukocyte, neutrophils, myeloperoxidase, nitric oxide, TNFalpha and IL-1beta levels (P<0.01) in the pleurisy induced by carrageenan. Passiflora edulis (250-500mg/kg, i.p.) also inhibited total and differential leukocytes in the pleurisy induced by bradykinin, histamine or substance P (P<0.05). CONCLUSION: Several mechanisms, including the inhibition of pro-inflammatory cytokines (TNFalpha, IL-1beta), enzyme (myeloperoxidase) and mediators (bradykinin, histamine, substance P, nitric oxide) release and/or action, appear to account for Passiflora edulis's actions.     

薯蓣皂苷元对小鼠下腔静脉结扎血栓形成及相关因子的影响

目的研究薯蓣皂苷元对静脉血栓形成的影响,并初步探讨其抗血栓作用的机理。方法通过小鼠下腔静脉结扎,测定形成血栓的重量及血清和血管壁内NO与MPO水平的变化。结果薯蓣皂苷元对小鼠下腔静脉结扎血栓形成具有抑制作用,能使血清中NO升高,而血管壁内的NO降低,MPO则升高。结论薯蓣皂苷元通过影响血液和血管壁内NO与MPO水平而发挥抗血栓形成作用。     

Grape seed extract treatment reduces hepatic ischemia-reperfusion injury in rats

This study was designed to determine the possible protective effect of grape seed extract (GSE), a widely used antioxidant dietary supplement, on hepatic ischemia/reperfusion (I/R) injury. Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by a 60 min reperfusion period. GSE was administered in a dose of 50 mg/kg/day orally for 15 days before I/R injury and repeated before the reperfusion period. Liver samples were taken for histological examination or determination of hepatic malondialdehyde (MDA), glutathione (GSH) and myeloperoxidase (MPO) activity. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Lactate dehydrogenase (LDH) and cytokines (TNF-alpha and IL-1 beta) were also assayed in serum samples for the evaluation of generalized tissue damage. Ischemia/reperfusion caused a significant decrease in hepatic GSH, and significant increases in MDA level, and MPO activity. Serum AST and ALT levels, as well as LDH activity and plasma TNF-alpha and IL-1beta levels were also elevated in the I/R group. Treatment with GSE reversed all these biochemical parameters as well as histological alterations induced by I/R. In conclusion, GSE reduced I/R-induced organ injury through its ability to balance the oxidant-antioxidant status, to inhibit neutrophil infiltration and to regulate the release of inflammatory mediators.     

黄芪提取物对大鼠全脑缺血再灌后炎症反应的影响

目的:探讨黄芪提取物对大鼠全脑缺血再灌后炎症反应的影响。方法:采用四血管阻塞法,复制大鼠全脑缺血再灌注模型;观察黄芪提取物对大鼠全脑缺血再灌后外周血白细胞和中性粒细胞计数、脑组织皮质和海马骨髓过氧化物酶(MPO)活性的影响;并对脑组织皮质做病理学检查。结果:与假手术组相比,模型组大鼠全脑缺血再灌注后外周血白细胞和中性粒细胞计数、脑组织皮质和海马MPO活性均明显升高;与模型组相比,黄芪提取物(20、40、80mg·kg-1)均可降低大鼠全脑缺血再灌注后升高的外周血白细胞和中性粒细胞计数、降低脑组织升高的皮质和海马MPO活性;改善脑组织皮质的缺血性改变。结论:黄芪提取物对大鼠全脑缺血再灌注损伤有明显的保护作用,其作用机制可能与其抗炎作用有关。     

二烯丙基三硫醚对脂多糖诱导小鼠肺炎的改善作用

目的探讨二烯丙基三硫醚(DATS)对脂多糖(LPS)诱导的小鼠肺炎的改善作用,并探讨其作用机制。方法小鼠随机分为对照组、模型组及DATS 20、40、80 mg/kg预防组和DATS 20、40、80 mg/kg治疗组。通过ip LPS制备小鼠急性肺炎模型,考察DATS对血清生化指标丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、炎症因子一氧化氮(NO)、细胞白介素8(IL-8)和肿瘤坏死因子α(TNF-α)、肺组织中髓过氧化物酶(MPO)、NO、NF-κB p65的影响。结果 DATS 40、80 mg/kg预防组和DATS 40、80 mg/kg治疗组能显著降低AST、NO、IL-8和TNF-α水平(P0.05),DATS 80 mg/kg预防组和DATS 80 mg/kg能显著降低LDH水平(P0.05),显著升高SOD水平(P0.05)。DATS 80 mg/kg预防组和DATS 80 mg/kg治疗组能显著升高MPO和NO水平(P0.05),并能抑制NF-κB p65的转移。结论 DATS对LPS诱导的肺部氧化损伤和炎症反应有一定的逆转作用,与DATS抑制NF-κB核转移和MPO活性有关。     

补心气口服液联合尼可地尔治疗冠心病心绞痛的临床研究

目的探讨补心气口服液联合尼可地尔治疗冠心病心绞痛的临床疗效。方法选取2017年6月—2018年6月在邯郸市第二医院治疗的冠心病心绞痛患者94例,根据住院号分为对照组(47例)和治疗组(47例)。对照组患者口服尼可地尔片,10 mg/次,3次/d;治疗组在对照组基础上口服补心气口服液,10 mL/次,3次/d。两组患者均治疗3个月。观察两组患者临床疗效,同时比较治疗前后两组患者心电图改善情况、心绞痛发作次数和持续时间及血清学指标。结果治疗后,对照组患者临床和心电图有效率分别为80.85%和82.98%,均分别显著低于治疗组的95.74%和97.87%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者心绞痛发作次数、持续时间较治疗前均显著降低(P0.05),且治疗组心绞痛发作次数和持续时间比对照组降低更明显(P0.05)。治疗后,两组血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)、髓过氧化物酶(MPO)和肌钙蛋白(CTnI)水平均显著降低(P0.05),且治疗后治疗组上述血清学指标水平明显低于对照组(P0.05)。结论补心气口服液联合尼可地尔治疗冠心病心绞痛能够明显改善患者心绞痛症状,降低机体炎症反应,降低心肌损害,具有一定的临床应用价值。