Prostaglandin involvement in hyperthermia induced by sleep deprivation: A pharmacological and autoradiographic study

AimsHyperthermia is a characteristic functional effect of sleep deprivation (SD). We hypothesize here that prostaglandin E2 (PGE2) could be involved in hyperthermia induced by sleep deprivation.Main methodsTo address this issue we examined the effects of a selective cyclo-oxygenase-2 inhibitor (COX-2) agent on hyperthermia induced by SD in rats. We also investigated binding to PGE2 receptors in hypothalamic brain areas of sleep-deprived rats using in vitro autoradiography. Male Wistar rats were deprived of sleep for 96 h using the platform technique. Sleep deprived and control groups received saline or Celecoxib (20, 30 and 40 mg/kg; p.o.) daily during the SD period. Colonic temperature was measured daily.Key findingsResults indicated that core temperature of sleep-deprived rats that receiving saline increased from the first to the fourth day of SD compared to baseline and to the respective control group. However, the hyperthermia induced by SD was not blocked by COX-2 inhibitor at any dose. [³H]PGE2 binding did not differ significantly among the groups in any of a number of hypothalamic areas examined.SignificanceAlthough SD rats showed no response to the COX-2 inhibitor and no alterations in [³H]PGE2 binding, the possibility remains that other prostaglandin system and/or receptor subtypes may be altered by SD.     

Blocking of urotensin receptors as new target for treatment of carrageenan induced inflammation in rats

This study investigated possible role of U-II and its receptor expression in inflammation by using UTR agonist and antagonist in carrageenan induced acute inflammation. Rats were divided into 5 groups as (1) Healthy control, (2) Carrageenan control, (3) Carrageenan +Indomethacin 20 mg/kg, orally, (4) Carrageenan +AC7954 (U-II receptor agonist, intraperitoneally) 30 mg/kg and (5) Carrageenan +SB657510 (UTR antagonist, intraperitoneally) 30 mg/kg. 1 h after drug administration, carrageenan was injected. At the 3rd hour after carrageenan injection, agonist produced no effect while antagonist 63% anti-inflammatory effect respectively. UTR and UT-II expression increased in carrageenan induced paw tissue. Antagonist administration prevented the decrease in an antioxidant system and also capable to decrease TNF-α and IL-6 mRNA expressions. This study showed the role of urotensin II receptors in the physiopathogenesis of acute inflammatory response that underlying many diseases accompanied by inflammation.     

刺槐素对大鼠心肌缺血再灌注损伤的保护作用与机制研究

摘要 目的：探讨刺槐素对大鼠心肌缺血再灌注损伤(MIRI)的作用以及可能的作用机制。方法：对24只Sprague-Dawley (SD)大鼠进行随机分组,分为：假手术组、模型组、刺槐素给药组、刺槐素+AG490给药组,每组6只,通过结扎冠状动脉左前降支,缺血30 min,再灌注120 min复制心肌缺血再灌注损伤模型。利用氯化三苯基四氮唑测定心肌梗死面积,紫外分光光度计和酶联免疫法检测血清中肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）的活性,蛋白印迹法分别检测心肌组织中Bcl-2、Bax、Stat3和p-Stat3蛋白相对表达水平。结果：与假手术组比较,模型组大鼠血清中CK-MB、LDH活性明显升高（P＜0.01）,心肌梗死面积百分比显著增加（P＜0.01）,p-Stat3/Stat3比率、Bcl-2/Bax比率显著下降（P＜0.01）;与模型组相比,刺槐素给药组中CK-MB、LDH的活性,以及心肌梗死面积百分比显著降低（P＜0.01）,Bcl-2/Bax比率和p-Stat3/Stat3比率显著提高（P＜0.05）。然而在刺槐素+AG490药物组中刺槐素对于受损心肌的保护作用被AG490消除。结论：刺槐素可减轻MIRI大鼠心肌损伤,发挥心肌保护作用,其机制可能与活化Jak2/Stat3信号通路进而抑制心肌细胞凋亡有关。     

Correlation of urinary inflammatory and oxidative stress markers in very low birth weight infants with subsequent development of bronchopulmonary dysplasia

Abstract

Currently, bronchopulmonary dysplasia (BPD) occurs almost exclusively in pre-term infants. In addition to prematurity, other factors like oxygen toxicity and inflammation can contribute to the pathogenesis. This study aimed to compare urinary inflammatory and oxidative stress markers between the no/mild BPD group and moderate/severe BPD group and between BPD cases with significant early lung disease like respiratory distress syndrome (RDS) (‘classic’ BPD) and with minimal early lung disease (‘atypical’ BPD). A total of 60 patients who were a gestational age < 30 weeks or a birth weight < 1250 g were included. Urine samples were obtained on the 1^st, 3^rd and 7^th day of life and measured the levels of leukotriene E₄ (LTE₄) and 8-hydroxydeoxyguanosine (8-OHdG). The 8-OHdG values on the 3^rd day showed significant correlation to duration of mechanical ventilation. The 8-OHdG levels on the 7^th day were the independent risk factor for developing moderate/severe BPD. In ‘classic’ BPD, the 8-OHdG values on the 3^rd day were higher than those of ‘atypical’ BPD. In ‘atypical’ BPD, the LTE₄ values on the 7^th day were higher than the values in ‘classic’ BPD. These results suggest that oxidative DNA damage could be the crucial mechanism in the pathogenesis of current BPD and the ongoing inflammatory process could be an important mechanism in ‘atypical’ BPD.     

Effects of Vitamin C and E Combination on Element and Oxidative Stress Levels in the Blood of Operative Patients Under Desflurane Anesthesia

We investigated effects of vitamin C and E (VCE) administration on desflurane-induced oxidative toxicity and element changes in the blood of operative patients under desflurane general anesthesia. Forty American Society of Anesthesiologists I or II Physical Status adult patients were scheduled for elective surgery. The patients were randomly divided into two groups. Control and VCE group was introduced to anesthesia with desflurane. VCE was administreted to patients in the control and VCE group before 1 hour of anesthesia with desflurane. Baseline (preoperative) and postoperative (at the 1^st, the 24^th, and 72^th h), blood samples were taken from the first and second groups. Erythrocyte and plasma lipid peroxidation levels at the 1^st, 24^th, and 72^th hours were higher in the control than in baseline group, although their levels at the same periods were lower in the VCE group than in the control. Vitamin E levels at the postoperative 1^st and 24^th hours and erythrocyte glutathione peroxidase (GSH-Px) activity at the postoperative 1^st, 24^th, and 72^th hours was lower than in baseline values. Erythrocyte GSH-Px activity and plasma vitamins A, C, and E levels at the postoperative 1^st, 24^th, and 72^th hours were higher in the VCE group than in the control group. Erythrocyte and plasma reduced glutathione, plasma β-carotene, and serum copper, while zinc, selenium, aluminum, iron, magnesium, and calcium levels did not differ between preoperative and postoperative periods in both groups. In conclusion, VCE combination prevented the desflurane-induced vitamin E and GSH-Px consumptions to strengthen the antioxidant levels in the blood of operative patients.     

两粤黄檀乙醇提取物化学成分分析及抗炎活性研究

为了研究壮药两粤黄檀的化学成分及其抗炎活性,阐明其药理作用机制,该研究采用小鼠二甲苯致炎耳廓肿胀法、角叉菜胶致炎足肿胀急性炎症模型,观察不同剂量两粤黄檀乙醇提取物对小鼠耳廓肿胀度、肿胀率及足肿胀度的影响,并利用液相色谱-质谱(LC-MS)、热裂解气相色谱-质谱(PY-GC/MS)等技术分析提取物的化学成分,结合网络药理学方法对其抗炎活性成分以及作用机制进行初步研究。结果表明:(1)两粤黄檀乙醇提取物具有良好的抗炎活性,高剂量组(8 g·kg~(-1))可以显著抑制二甲苯致小鼠耳廓肿胀度、角叉菜胶致炎足趾肿胀,其抑制率均高于50%;(2)从两粤黄檀乙醇提取物中共鉴定得到60个化合物,包括毛蕊异黄酮、芒柄花黄素、血根碱、胡椒碱、β-谷甾醇等多种抗炎活性成分;(3)网络药理学分析显示,两粤黄檀发挥抗炎作用的核心靶点为PIK3CA、EGFR、MAPK、SRC、STAT3、CYP19A1、IL2、MAOA等,涉及c GMP-PKG、cAMP、Focal adhesion、Rap1等信号通路。该研究结果为两粤黄檀的进一步开发利用提供了重要参考。     

Hesperidin attenuates inflammation and oxidative damage in pleural exudates and liver of rat model of pleurisy

Objectives: This study investigated the potential anti-inflammatory effect of hesperidin against carrageenan induced pleurisy in rat model.

Methods: Twenty-four adult female Wistar rats (350 - 450g) were grouped as follows: Group I: rats were administered saline solution only (Normal control group); Group II: rats were administered saline solution (NaCl 0.9%) orally and injected with carrageenan (Inflammation control group); Group III: rats were administered hesperidin only (Hesperidin group); Group IV: rats were administered hesperidin orally and intrapleurally injected with 2% carrageenan (Inflammation treated with hesperidin group). The exudate volume, total leukocyte count, reactive oxygen species (ROS), myeloperoxidase (MPO),δ–aminolevulinate dehydratase (δ-ALA-D), catalase (CAT), superoxide dismutase (SOD), activities as well as non-protein thiol group (NPSH) and thiobarbituric acid reactive substances (TBARS) levels were determined.

Results: Pretreatment with hesperidin at a dose of 80 mg/kg orally per day for 21 days, minimized the increase in pleural exudate volume and leucocyte count and modulated the activities of MPO, SOD and CAT, as well as the levels of ROS, NPSH and TBARS in carrageenan-induced rats.

Conclusion: Our results suggest that hesperidin can elicit its anti-inflammatory action by blocking exudate and leukocyte influx into pleural cavity, inhibiting MPO activity and preventing oxidative damage.     

Inhibitory effect of quercetin on carrageenan-induced inflammation in rats

We examined the effect of quercetin on the inflammatory response induced by carrageenan in the rat. Air pouches were induced subcutaneously on the backs of rats and injected with carrageenan. The rats were treated with either vehicle or quercetin at a dose of 10 mg/kg one hour before carrageenan challenge. Fourty-eight hour after carrageenan challenge, the air pouches were removed and analyzed. The volume, protein amounts and cell counts in the exudation obtained from the quercetin-treated animals were significantly reduced compared to those from vehicle-treated animals. The contents of PGE(2), TNF-alpha, RANTES, MIP-2 and the mRNA for cyclooxygenase-2 were also suppressed in these rats. The histological examination displayed the suppression of the inflammatory response in the pouch tissues from quercetin-treated rats. As the anti-inflammatory effect of the flavonols was more or less at the similar level among the quercetin-, isoquercitrin- or rutin-treated rats, it appeared that the sugar parts did not influence on the anti-inflammatory effect.Our study indicated that the flavonols modulated the inflammatory response, at least in part, by modulating the prostanoid synthesis as well as cytokine production.     

孔腔镜肺叶切除及淋巴结清扫术围手术期应用不同剂量氨溴索对肺癌患者的作用研究

摘要 目的：探讨围手术期应用不同剂量氨溴索对行单孔腔镜肺叶切除及淋巴结清扫术的肺癌患者的作用。方法：选取本院2017年1月至2018年12月期间收治的124例肺癌患者作为受试者,结合患者意愿按随机数字表法将受试者分为小剂量组（n=41）、中剂量组（n=41）和大剂量组（n=42）,术前1d开始给予氨溴索静脉滴注,术后持续7d,比较各组患者临床症状、治疗前后的肺功能、炎症因子、T细胞亚群水平变化及不良反应发生率。结果：大剂量组咳痰容易人数所占比例高于小剂量组,痰液稀薄人数所占比例高于中剂量组及小剂量组（P<0.05）。治疗后大剂量组第一秒用力呼吸容积（FEV¹）、FEV¹/用力肺活量（FVC）高于中剂量组、小剂量组（P<0.05）。治疗后各组炎症因子水平均高于治疗前,且随着剂量的升高,C反应蛋白（CRP）、白介素-6（IL-6）、白介素-8（IL-8）水平呈降低的趋势（P<0.05）。随着剂量的升高,治疗后的 CD3⁺、CD4⁺、CD4⁺/CD8⁺均呈升高趋势,CD8⁺呈降低趋势（P<0.05）。各组不良反应发生率比较无统计学差异（P>0.05）。结论：肺癌患者行单孔腔镜肺叶切除及淋巴结清扫术围手术期应用120mg氨溴索,可加快患者术后恢复,保护患者肺功能,抑制炎症反应,改善患者的免疫功能和临床症状。     

Effects of Chronic Ethanol Administration on Serotonin Metabolism in the Various Regions of the Rat Brain

Changes in serotonin (5-HT) and 5-hydroxy indole acetic acid (5-HIAA), its major metabolite, in cerebral cortex, corpus striatum and hippocampus were investigated at 10^th and 21^st days of chronic ethanol ingestion in Wistar rats. Ethanol (7.2% v/v) was given to rats in a modified liquid diet. Biochemical analysis was performed in two groups of ethanol-treated and control rats (n = 6 for each group). Rats in each group were decapitated at the 10^th and 21^st days of ethanol consumption. Brains were removed and cerebral cortex, corpus striatum and hippocampus were dissected. 5-HT and 5-HIAA levels were measured in respective brain regions by using high performance liquid chromatography. In cerebral cortex and corpus striatum, 5-HT levels were significantly lower than control at the 10^th day of ethanol consumption. At the 21^st day, the levels tended to remain low, but not significantly different statistically. In hippocampus, 5-HIAA levels were significantly higher than control at 10^th day of ethanol consumption. Increased 5-HIAA level returned to control values at the 21^st day of ethanol consumption. Our results suggest that, 5-HT clearly seems to play a critical role in the brain at the 10^th day of chronic ethanol consumption.