黄芩苷改善肿瘤缺氧微环境抑制乳腺癌移植瘤的生长＊

目的 通过观察黄芩苷对乳腺癌组织毛细血管通透性（Capillary Vessel Permeability，CVP）、赖氨酰氧化酶（Lysyl Oxidase，LOX）及血清丙二醛（Malondialdehyde，MDA）等相关指标的影响，探讨黄芩苷可能的抗乳腺癌作用机制。方法 通过在裸鼠皮下接种MDA-MB-231乳腺癌细胞株建立乳腺癌移植瘤模型；实验分为模型组、黄芩苷组、阿霉素组、黄芩苷+阿霉素组。于接种第7日开始：黄芩苷组每天灌胃黄芩苷水溶液（100 mg·kg^-1），连续14天；阿霉素组每3天腹腔注射一次阿霉素（5mg·kg^-1），共用药5次；模型组每天灌胃生理盐水（10 mL·kg^-1），连续14天；黄芩苷+阿霉素组每天灌胃黄芩苷水溶液（100 mg·kg^-1），连续14天，并每3天腹腔注射一次阿霉素5 mg·kg^-1，共5次。给药期间监测移植瘤体积；紫外可见分光光度计620 nm下测OD值来反映黄芩苷对肿瘤毛细血管通透性的影响；硫代巴比妥酸（Thiobarbituric acid，TBA）比色法检测黄芩苷对裸鼠血清中丙二醛（MDA）的影响；免疫组化染色法检测乳腺癌组织中赖氨酰氧化酶（LOX）的表达情况。结果 ①与模型组比较，黄芩苷组、阿霉素组、黄芩苷+阿霉素组瘤体重量均明显减轻（P<0.05）；黄芩苷+阿霉素组瘤体重量较阿霉素组明显减轻（P<0.05）。②与模型组比较，黄芩苷组降低乳腺癌组织毛细血管的通透性，而阿霉素组则增加肿瘤组织中毛细血管的通透性，差异均具有统计学意义（P<0.05）。③黄芩苷组能够明显抑制荷瘤裸鼠血清MDA的表达，与模型组比较差异有显著统计学意义（P<0.01）；阿霉素组促进MDA的表达，与模型组比较差异有统计学意义；黄芩苷+阿霉素组促进MDA的表达，与模型组比较差异无统计学意义。④与模型组比较，黄芩苷组裸鼠乳腺癌组织LOX的表达显著下调（P<0.01），阿霉素组肿瘤组织中LOX表达增加（P<0.05）；黄芩苷+阿霉素组能下调裸鼠乳腺癌组织LOX的表达，与模型组比较差异无统计学意义。结论 黄芩苷能够明显抑制乳腺癌移植瘤的生长，其机制可能与黄芩苷降低肿瘤组织毛细血管的通透性，抑制裸鼠血清中丙二醛、乳腺癌组织中赖氨酰氧化酶的表达，从而改变肿瘤缺氧微环境有关。     

Impact of Cinnamon Supplementation on cardiometabolic Biomarkers of Inflammation and Oxidative Stress: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background & objectiveTo date, cinnamon supplementation has been investigated due to its antioxidant and anti-inflammatory properties. Several studies have confirmed the effects of cinnamon supplementation on several markers of cardiometabolic health. However, the effects of cinnamon supplementation on inflammation and oxidative stress levels warrant further investigation. Hence, the current meta-analysis was conducted to elucidate the impact of cinnamon supplementation on biomarkers of inflammation and oxidative stress.MethodsTo perform this systematic review and meta-analysis, we employed the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic search of available clinical trials was performed using the following databases: PubMed/MEDLINE, Scopus, Cochrane Library, Web of Science, Embase, and Google Scholar, up to January 2020.ResultsAfter removing the duplicates, 1145 studies were eligible for analysis and 12 of them were included in the meta-analysis. The dose of cinnamon powder investigated in the included trials ranged from 1.5 to 4 g/day. Cinnamon supplementation resulted in a significant reduction of C-reactive protein (CRP) (weight mean difference (WMD): −2.22 mg/L, 95 % CI: −3.74, −0.69, P = 0.004) and malondialdehyde (MDA) (WMD: −0.79 mmol/L, 95 % CI: −1.28, −0.29, P = 0.002), and marginally statistical significant decrease in interleukin-6 (IL-6) (WMD: −1.48 pg/mL, 95 % CI: −2.96, −0.01, P = 0.049). Moreover, it was associated with an increase in the total antioxidant capacity (TAC) (WMD: 0.34 mmol/L, 95 % CI: 0.04, 0.64, P = 0.026). However, the levels of intercellular adhesion molecule-1 (ICAM-1) (WMD: 1.53 ng/mL, 95 % CI: −12.03, 15.10, P = 0.82) did not change significantly following cinnamon supplementation.ConclusionsCinnamon supplementation may be an adjuvant for reducing inflammation and oxidative stress levels in humans.     

外源性胆绿素对中波紫外线诱导的角质形成细胞光损伤的保护作用和机制

【摘要】 目的 探讨外源性胆绿素对中波紫外线（UVB）照射的HaCaT细胞光损伤的保护作用。方法 将HaCaT细胞分为加入0、0.1、1、10 μmol/L胆绿素并照射UVB的UVB组、0.1 μmol/L UVB组、1 μmol/L UVB组、10 μmol/L UVB组及不做处理的对照组。UVB照射剂量为30 mJ/cm2，照射后继续培养24 h，分别检测细胞活性氧（ROS）水平、超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量，ELISA法检测各组细胞的炎症因子白细胞介素6（IL-6）、IL-8水平。多组间均数比较采用单因素方差分析，组间两两比较采用LSD-t检验。结果 UVB组、0.1 μmol/L UVB 组、1 μmol/L UVB组、10 μmol/L UVB组、对照组细胞ROS水平（3 613.33 ± 206.61、2 958.67 ± 193.87、2 678.33 ± 178.24、2 274.67 ± 118.81、1 905.67 ± 250.25）、SOD活力（24.41 ± 1.78、28.96 ± 2.21、29.75 ± 1.75、30.19 ± 2.29、37.52 ± 2.31）、MDA含量（5.61 ± 0.32、5.46 ± 0.55、4.65 ± 0.22、2.55 ± 0.93、1.31 ± 0.05）、IL-6水平、IL-8水平差异均有统计学意义（F值分别为 34.02、57.36、214.09、29.73、11.40，均P < 0.05），UVB组ROS水平、MDA含量及IL-6、IL-8水平均高于另4组（均P < 0.05），SOD活力均低于另4组（均P < 0.05）。结论 外源性胆绿素减轻UVB引起的HaCaT细胞的氧化损伤、减轻炎症反应和抑制脂质过氧化作用，对细胞光损伤有一定的保护作用。     

Increased oxidative stress and damage in patients with chronic bacterial prostatitis

Objective To investigate whether chronic bacterial prostatitis （CBP） increases oxidative stress and damage in patients with CBP, and to explore its possible mechanism. Methods Eighty patients with CBP and 80 healthy adults as controls were enrolled in a case-control study, in which levels of nitric oxide （NO）, vitamin C （VC）, and vitamin E （VE） in plasma, as well as malondialdehyde （MDA）, activities of superoxide dismutase （SOD）, and eatalase （CAT） in erythrocytes were determined by spectrophotometry. Results Compared with the average values of NO, VC, VE, MDA, SOD, and CAT in the healthy control group, those of plasma N O and erythrocyte MDA in the CBP group were significantly increased （P〈0.00 1）, and those of plasma VC and VE as well as erythrocyte SOD and CAT in the CBP group were significantly decreased （P〈0.001）. Findings from partial correlation analysis for course of the disease and NO, VC, VE, MDA, SOD, and CAT in 80 patients with CBP, adjusted for age, suggested that with prolonged course of the disease, values of NO and MDA were gradually increased （P〈0.001）, and those of VC, VE, SOD, and CAT were gradually decreased （P〈0.05-0.001）. The findings from stepwise regression analysis for course of the disease and NO, VC, VE, MDA, SOD, and CAT in CBP group suggested that the model of stepwise regression was Y = -19.1160 ＋0.3112MDA ＋ 0.0337NO, F = 22.1734, P〈0.001, r = 0.6045, P〈0.001. The findings from the reliability analysis for VC, VE, SOD, CAT, NO, and MDA in the CBP group showed that the reliability coefficients＇ alpha （6 items） was 0.7195, P〈0.0001, and the standardized item alpha was 0.9307, P〈0.0001. Conclusion There exist increased oxidative stress and damage induced by chronic bacterial prostatitis in patients, and such a phenomenon is closely related to the course of disease.     

Changes of serum Tau, GFAP, TNF-α and malonaldehyde after blast-related traumatic brain injury

Objective： To determine the changes of serum Tau protein, glial fibrillary acidic protein （GFAP）, tumor necrosis factor alpha （TNF-α）, and malonaldehyde （MDA） in rats after blast-related traumatic brain injury （BTBI） and to provide relative information for further studies on BTBI mechanism and seek specific biomarkers for BTBI. Methods： Ninety male Sprague-Dawley rats were randomly assigned into three groups： control group, moderate blast injury group, and severe blast injury group （n=30 for each）. Rats in the moderate and severe blast injury groups were respectively exposed to corresponding levels of BTBI. After explosion, serum levels of Tau, GFAP, TNF-α, and MDA in each group were determined by Elisa assay at different time points after injury （8 h, 24 h, 3 d, and 6 d）. The extent of brain damage was detected by Nissl staining and TUNEL assay. Results： Serum levels of Tau and GFAP rapidly increased and reached the peak at 24 h after either moderate or severe blast injury. All the values were significantly higher than control group at all time points （P〈0.05）. Serum TNF-α level of both injury groups peaked at 8 h after BTBI and stayed significantly higher than control group at all time points （P〈0.05）. Serum MDA of two injury groups began to significantly increase at 3 d and the level stayed significantly higher than control group until 6 d （P〈0.05）. Moreover, unlike the other biomarkers, serum MDA of severe blast injury group was significantly higher than moderate blast injury group at 6 d （P〈0.05）. Conclusion： The changes of serum Tau, GFAP, and TNF-α showed a good sensitivity at the acute phase after BTBI （within 24 h）. However, their specificity and correlation with the extent of injury were limited in this experiment. Moreover, although the change of serum MDA showed a poor sensitivity and specificity to the diagnosis of BTBI during the first few days, it can reflect the injury degree at 6 d after injury. Therefore, further studies are nee     

二甲氨基乙醇和复方氨基酸溶液对衰老 大鼠皮肤胶原代谢和自由基的影响

目的 探讨真皮内注射二甲氨基乙醇（DMAE）和复方氨基酸溶液（AA）对皮肤胶原代谢和自由基的影响.方法 80只大鼠随机分成衰老治疗组（60只）、衰老对照组（10只）和正常对照组（10只）.皮下注射半乳糖制备衰老模型.衰老治疗组从第18天开始,在两侧臀部真皮内分别注射0.2％ DMAE＋AA、0.1％ DMAE＋AA、0.2％ DMAE、0.1％ DMAE、AA、生理盐水（NS）,每周1次,连续4周.观察各组皮肤苏木精-伊红染色法（HE）切片组织学变化并测定皮肤中含水量、超氧化物歧化酶（SOD）活力、羟脯氨酸（HYP）和丙二醛（MDA）含量.结果 0.2％DMAE＋ AA组、0.1％ DMAE＋AA组表皮、真皮厚度和胶原纤维面积均高于衰老对照组,差异有统计学意义（P＜0.05）.0.2％ DMAE＋AA组、0.1％ DMAE＋ AA组与其他各衰老组相比,HYP含量增加、SOD活力升高、MDA含量降低,其组间差异具有统计学意义（P＜0.05）.正常对照组、0.2％ DMAE＋AA组、0.1％DMAE＋ AA组之间HYP含量差异无统计学意义（P＞0.05）.各组大鼠皮肤含水量差异无统计学意义（P＜0.05）.结论 真皮内注射0.2％ DMAE＋AA、0.1％ DMAE＋AA能显著增加表皮、真皮厚度和胶原纤维面积及HYP含量,提高SOD活力、降低MDA含量,表明其有清除皮肤自由基、提高抗氧化能力和促进皮肤胶原代谢的作用,从而延缓皮肤衰老.     

The effects of iloprost on ischemia-reperfusion injury in skeletal muscles in a rodent model

Purpose

The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model.

Materials and methods

Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses.

Results

Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL.

Conclusions

These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model.     

Aging aggravates long-term renal ischemia-reperfusion injury in a rat model

Aim

Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI.

Materials and methods

Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF-β1) and messenger RNA level of TGF-β1 in the kidney were analyzed.

Results

Renal IRI caused significant increases of malondialdehyde and 8-hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-β1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI.

Conclusion

Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI.     

不同幅度脉冲膈肌起搏对兔膈肌SOD、MDA、总抗氧化能力的影响

目的　探讨不同幅度脉冲膈肌起搏 (diaphragmpacing ,DP)对新西兰大白兔膈肌的影响。方法　建立兔颈部DP模型 ,测定无起搏 (A)组及脉冲幅度匀速增加 (B)组、恒定 (C)组、匀速减小 (D)组起搏后膈肌组织SOD、MDA及T AOC。结果　①DP后 ,B组较A组MDA含量增加 ,SOD及T AOC减小 (P >0 .0 5 ) ;②DP后 ,C组及D组较A组MDA含量增加 ,SOD及T AOC减小 (P <0 .0 5 ) ;③DP后 ,B组较C及D组MDA含量少 ,SOD及T AOC活力强 (P <0 .0 5 )。结论　①脉冲幅度匀速增加通过减少氧自由基的产生 ,抗氧化能力的干扰 ,可能减缓了膈肌疲劳 (diaphragmfailure ,DF)的发生 ,②脉冲幅度匀速增加与脉冲幅度恒定和匀速减小相比 ,是一种更为合理的DP方式。     

Effects of high-voltage electrical burns and other burns on levels of serum oxidative stress and telomerase in children

Introduction

Electrical burns cause significant morbidity and mortality worldwide. Here we measured changes in levels of serum oxidative stress and telomerase in children suffering from high-voltage electrical burn (HVEB) injuries and other burns and the significance of these parameters in terms of amputation.