Dysregulated Hepatic Expression of Glucose Transporter Type-1,Toll-Like Receptor 4,and Nuclear Factor Kappa B in Estrogen-Induced Cholestasis Pregnant Rats with Placental Ischemia-Reperfusion Stress

Objective:This study aimed at investigating the expression of nuclear factor kappa B(NF-κB)and mammalian target of rapamycin(mTOR)related signal pathways in liver tissues of intrahepatic cholestasis of pregnancy animal models.Methods:Estrogen(EE)-induced cholestasis and a placental ischemia-reperfusion(IR)model were established in pregnant rats.All pregnant rats were divided into four groups by random number table:EE-IR group(n=6),EE-sham group(n=6),control-IR group(n=6)and control-sham group(n=6).Liver expression of mTOR,its upstream regulator DNA damage response-1(REDD1),and downstream factor glucose transporter type-1(GLUT1),accompanied by NF-κB(p65 is the most important component),its activator toll-like receptor 4(TLR4),and inhibitor IκBα,were detected by western blot analysis and real-time polymerase chain reaction.The intergroup comparisons were performed with a one-way analysis of variance,the comparisons among groups were analyzed with the nonparametric Kruskal-Wallis test.Results:Giving pregnant rats EE alone reduced the hepatic expression of IκBα(0.72±0.20vs.1.01±0.07,P=0.008).Meanwhile,giving pregnant rats placental IR alone increased liver levels of REDD1(3.24±0.98vs.1.06±0.24,P=0.025),GLUT1(2.37±0.82vs.1.09±0.10,P=0.039),TLR4(2.12±0.29vs.1.20±0.28,P=0.010),and p65(2.09±0.85vs.1.04±0.06,P=0.023),and decreased hepatic mTOR(0.50±0.07vs.1.01±0.03,P=0.001)and IκBα(0.61±0.08vs.1.01±0.07,P=0.014)expression.Subjecting EE-treated rats to placental IR did not further alter liver levels of GLUT1(2.02±0.45vs.1.79±0.39,P=0.240),TLR4(2.10±0.74vs.1.60±0.36,P=0.129),or p65(2.41±0.83vs.1.65±0.46,P=0.145),whereas it did decrease hepatic mTOR(0.42±0.09vs.0.90±0.14,P=0.008)and IκBα(0.43±0.09vs.0.72±0.20,P=0.004)expression and enhance REDD1 expression(4.46±0.65vs.2.05±0.47,P=0.009).Placental IR stress did impact the hepatic expression of REDD1-mTOR-GLUT1 and TLR4/NF-κB/IκBαin pregnant rats.Conclusion:Placental IR-induced hepatic GLUT1,TLR4,and p65 alternation,which responded efficiently in control rats,were impaired in EE-induced ICP rats.     

高浓度氧致新生鼠肝组织总抗氧化能力与丙二醛含量变化的动态研究

目的 研究新生鼠吸入高浓度氧后,不同时间内肝组织总抗氧化能力(total antioxidative capaciry,TAOC)及丙二醛(malonidi-aldehyde,MDA)含量的变化,探讨吸入高浓度氧是否能导致新生鼠肝脏损伤.方法 生后12h内的64只足月新生鼠作为研究对象,随机分为高氧组(FiO2=0.85,n=32)和对照组(空气,n=32).每组分别于1d、3d、7d、14d随机处死8只新生鼠分离肝组织,采用化学比色法检测肝组织匀浆中TAOC、硫代巴比妥酸法检测肝组织匀浆中MDA含量.结果 高浓度氧暴露1d时,新生鼠肝组织TAOC升高[(3.60±0.28)U/mg prot vs (3.39±0.19)U/mg prot,P<0.05];高浓度氧暴露3d,肝组织TAOC逐渐降低;14d时仍较对照组显著降低[(3.10±0.15)U/mg prot vs(3.56±0.14)U/mg prot],差异有统计学意义(P<0.01).MDA含量于高浓度氧暴露3d时开始升高[(3.58±0.11)nmol/mg prot (2.82±0.135)nmol/mg prot,P<0.01];7d时显著高于对照组[(3.58±0.11)nmol/mg prot vs(2.82±0.135)nmol/mg prot,P<0.01];暴露14d时MDA含量虽有所下降,但仍显著高于对照组[(2.92±0.19)nmol/mg prot vs(2.77±0.09)nmol/mg prot,P<0.01].结论 新生鼠吸入高浓度氧后肝组织TAOC的降低及过量的MDA生成可导致肝脏损伤.随着吸入高浓度氧时间的延长,肝脏损伤的程度加重.

Abstract：

Objective To determine the levels of total antioxidative capacity(TAOC) and malondialdehyde(MDA) in liver exposed to hyperoxia,and to explore whether oxygen inhalation could cause liver injury in newborn rats.Methods Sixty-four newborn rats which were less than 12-hour-old were enrolled in this study.The rats were randomly divided into hyperoxia group(FiO2=0.85,n=32) and control group(air,n=32).Eight rats in each group were randomly sacrificed to obtain liver tissues at 1d,3d,7d and 14d.The TAOC of liver homogenates was detected by chemical colorimetry,and the MDA level of liver homogenates was measured by thiobarbituric acid test.Results In the hyperoxia group,TAOC in liver increased on the 1st day[(3.60±0.28)U/mg prot vs(3.39±0.19)U/mg prot,P<0.05];TAOC began to decreased on the 3rd day,and significantly lower than that of control group on the 14th day [(3.10±0.15)U/mg prot vs (3.56±0.14)U/mg prot,P<0.01].In the hyperoxia group,the MDA level increased on the 3rd day[(3.58±0.11)nmol/mg prot vs(2.82±0.14)nmol/mg prot,P<0.01],and reached a peak on the 7th day[(3.58 ±0.11)nmol/mg prot vs(2.82±0.14)nmol/mg prot,P<0.01],then decreased but still remained higher than control group on the 14th day [(2.92±0.18)nmol/mg prot vs(2.77 ±0.09)nmol/mg prot,P<0.01].Conclusion Too more MDA in liver and TAOC decrease may cause liver injury in newborn rats exposed to hyperoxia.With the oxygen inhalation time prolonging,the liver injury aggravation.     

白藜芦醇对大鼠肠缺血再灌注致肠黏膜通透性改变的影响

目的 探讨白藜芦醇(RES)对肠缺血再灌注致肠黏膜损伤大鼠的保护作用及其可能机制.方法 成年雄性SD大鼠24只随机分为假手术组、缺血再灌注损伤组、RES治疗组.假手术组仅分离肠系膜上动脉(SMA)而根部不夹闭.肠缺血再灌注损伤组和RES治疗组均用无损伤血管夹夹闭SMA根部,分别立即经阴茎背静脉注射9g·L-1盐水、RES( 20 mg·kg-1),45 min后放松血管夹形成再灌注.各组大鼠均于制模后6h采集静脉血和回肠标本.检测血清二胺氧化酶(DAO)及小肠脂肪酸结合蛋白(IFABP)水平,应用原位末端转移酶标记法检测肠黏膜上皮细胞凋亡率,HE染色法观察肠组织病理损伤情况.结果 肠缺血再灌注6h后,RES治疗组DAO及IFABP水平与肠缺血再灌注损伤组比较显著减少[DAO:(1 650±1 150)U·L-1vs(2920±1 520)U·L-1;IFABP:(845.12±123.86) μg·L-1vs(1 443.76±174.62) μg·L-1,Pa＜0.05],但二组较假手术组[(630±150)U·L-1,(26.76±4.86)μg·L-1)]均显著增加(Pa＜0.05).假手术组大鼠肠绒毛顶部、固有层和黏膜下层只有少量散在分布的凋亡细胞,缺血再灌注损伤组大鼠肠黏膜凋亡阳性细胞数量较假手术组明显增加[(66.63±1.71)％ vs (9.60±1.76)％,P＜0.05],分布范围从绒毛顶部扩大到中、底部,固有层和黏膜下层,细胞凋亡亦明显加重;RES组大鼠肠黏膜细胞凋亡率[(46.72±1.50)％]明显低于缺血再灌注损伤组(P＜0.05).结论 RES对肠缺血再灌注损伤具有保护作用,其机制可能与其抑制肠黏膜上皮细胞凋亡有关.     

Changes of B cell - activating factor and a proliferation - inducing ligand in serum of children with Henoch -Schonlein purpura nephritis北大核心CSCD

Objective To investigate the changes of B cell - activating factor (BAFF) and a proliferation -inducing ligand (APRIL) in serum of children with Henoch - Schonlein purpura nephritis (HSPN), and to explore their role in the pathogenesis of children HSPN. Methods A total of 28 children with HSPN who were before treatment were selected in Department of Pediatrics Nephrology and Rheumatology,Shengjing Hospital of China Medical University from November 2017 to August 2018. Sixteen children with Henoch - Schonlein purpura were selected as HSP group, and 20 healthy children were selected as healthy control group. Followed the HSPN guideline to cure the patients for 6-8 weeks. The clinical data were collected. Serum levels of BAFF and APRIL were measured by adopting enzyme -linked immunosorbent assay (ELISA). Results (1) Changes of serum BAFF level: the serum levels of BAFF in HSPN children were significantly lower than those in the HSP group and the healthy control group [HSPN group (0. 652 ± 0.360) |jLg/L,HSP group (1.276 ±0.459) |jig/L, healthy control group (1. 285 ± 0. 299) |jLg/L, F = 17. 519,P = 0.000]. Moreover, the serum levels of BAFF in before treatment were significantly lower than those in after treatment [before treatment (0. 652 ± 0. 360) |JLg/L, after treatment (0. 860 ±0. 262) |JLg/L, P < 0. 05). However, there were no significant di-fferences in the serum levels of BAFF between HSP group and healthy control group (P >0.05). (2)Changes of serum APRIL level: the serum levels of APRIL in HSPN and HSP children were both significantly higher than those in healthy control group,but there were no marked differences between the 2 groups [HSPN group (2.285 ±1.015) |JLg/L, HSP group (2.609 ±1.264) |jig/L, healthy control group (1.677 ±0. 118) |JLg/L,F =3. 647,P =0. 016]. There were no significant differences in the serum levels of APRIL between before treatment and after treatment [before treatment (2. 285 ±1.015) |JLg/L, after treatment (2. 042 ± 0. 695) |Jig/L, P > 0. 05]. (3) Pearson correlation analysis results showed that the serum levels of BAFF were negatively correlated with 24 h urinary protein, urinary microalbumin, and urine red blood cell count (r = -0. 587, -0.608, -0.515,all P <0. 05). The serum levels of APRIL were positively correlated with serum IgA(r = 0. 588,P < 0. 05). Conclusions The level of serum BAFF decreased and APRIL increased in children with HSPN, which was related to the degree of renal involvement. It suggests that BAFF and APRIL may be related to the pathogenesis of HSPN in children. © 2019 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.     

Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism北大核心CSCD

Objective To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism. Methods A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg) +ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats. Results Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05). Conclusions Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury. © 2023 Xiangya Hospital of CSU. All rights reserved.     

糖尿病酮症酸中毒患儿氧化应激状况及影响因素分析

Objective To investigate the oxidative stress state in children with diabetic ketoacidosis (DKA),and analyze whether any observed abnormalities were related to metabolic disturbances.Methods Four groups of subjects were studied,comprising with 22 patients with DKA(group 1),18 diabetic children with medium metabolic control,whose glycated hemoglobin(HbAlc) below 9%(group 2),22 children with poorly controlled diabetes,whose Hbal c above 9%(group 3),and 36 healthy control children(group 4).Malondialdehyde(MDA),nitrate oxidase(NO),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and metabolic parameters such as fasting blood glucose,HbAlc,blood gas analysis,serum ion,renal function of the subjects were measured.Results Mean serum MDA value was significantly higher in group 1 than in group 2(P ＜0.01) and group 4(P ＜0.01),but was not different from that in group 3 (P ＞0.05).Serum levels of NO were significantly higher in group 1,2 and 3 compared with group 4(P＜0.01).Serum levels of GSH-Px were significantly lower in group 1,2 and 3 than in group 4(P＜0.01).There were no significant differences of serum SOD value among the four groups(P＞0.05).Both serum MDA and NO values in the diabetic patients(groups 1 +2 +3) were positively related to HbAlc(r=0.375,P ＜0.01;r=0.250,P ＜0.05),and serum SOD values in the DKA patients were negatively related to HbAlc(r= -0.507,P＜0.05),there were not any significant relationship between the other oxidative markers and metabolic parameters.Conclusion There is an increase of oxidative stress and decrease of antioxygenic ability in DKA children,and these changes tend to correlate more with markers of diabetic imbalance than with parameters of acute metabolic disturbances of DKA.     

糖尿病酮症酸中毒患儿氧化应激状况及影响因素分析

Objective To investigate the oxidative stress state in children with diabetic ketoacidosis (DKA),and analyze whether any observed abnormalities were related to metabolic disturbances.Methods Four groups of subjects were studied,comprising with 22 patients with DKA(group 1),18 diabetic children with medium metabolic control,whose glycated hemoglobin(HbAlc) below 9%(group 2),22 children with poorly controlled diabetes,whose Hbal c above 9%(group 3),and 36 healthy control children(group 4).Malondialdehyde(MDA),nitrate oxidase(NO),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and metabolic parameters such as fasting blood glucose,HbAlc,blood gas analysis,serum ion,renal function of the subjects were measured.Results Mean serum MDA value was significantly higher in group 1 than in group 2(P ＜0.01) and group 4(P ＜0.01),but was not different from that in group 3 (P ＞0.05).Serum levels of NO were significantly higher in group 1,2 and 3 compared with group 4(P＜0.01).Serum levels of GSH-Px were significantly lower in group 1,2 and 3 than in group 4(P＜0.01).There were no significant differences of serum SOD value among the four groups(P＞0.05).Both serum MDA and NO values in the diabetic patients(groups 1 +2 +3) were positively related to HbAlc(r=0.375,P ＜0.01;r=0.250,P ＜0.05),and serum SOD values in the DKA patients were negatively related to HbAlc(r= -0.507,P＜0.05),there were not any significant relationship between the other oxidative markers and metabolic parameters.Conclusion There is an increase of oxidative stress and decrease of antioxygenic ability in DKA children,and these changes tend to correlate more with markers of diabetic imbalance than with parameters of acute metabolic disturbances of DKA.     

糖尿病酮症酸中毒患儿氧化应激状况及影响因素分析

Objective To investigate the oxidative stress state in children with diabetic ketoacidosis (DKA),and analyze whether any observed abnormalities were related to metabolic disturbances.Methods Four groups of subjects were studied,comprising with 22 patients with DKA(group 1),18 diabetic children with medium metabolic control,whose glycated hemoglobin(HbAlc) below 9%(group 2),22 children with poorly controlled diabetes,whose Hbal c above 9%(group 3),and 36 healthy control children(group 4).Malondialdehyde(MDA),nitrate oxidase(NO),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and metabolic parameters such as fasting blood glucose,HbAlc,blood gas analysis,serum ion,renal function of the subjects were measured.Results Mean serum MDA value was significantly higher in group 1 than in group 2(P ＜0.01) and group 4(P ＜0.01),but was not different from that in group 3 (P ＞0.05).Serum levels of NO were significantly higher in group 1,2 and 3 compared with group 4(P＜0.01).Serum levels of GSH-Px were significantly lower in group 1,2 and 3 than in group 4(P＜0.01).There were no significant differences of serum SOD value among the four groups(P＞0.05).Both serum MDA and NO values in the diabetic patients(groups 1 +2 +3) were positively related to HbAlc(r=0.375,P ＜0.01;r=0.250,P ＜0.05),and serum SOD values in the DKA patients were negatively related to HbAlc(r= -0.507,P＜0.05),there were not any significant relationship between the other oxidative markers and metabolic parameters.Conclusion There is an increase of oxidative stress and decrease of antioxygenic ability in DKA children,and these changes tend to correlate more with markers of diabetic imbalance than with parameters of acute metabolic disturbances of DKA.     

糖尿病酮症酸中毒患儿氧化应激状况及影响因素分析

Objective To investigate the oxidative stress state in children with diabetic ketoacidosis (DKA),and analyze whether any observed abnormalities were related to metabolic disturbances.Methods Four groups of subjects were studied,comprising with 22 patients with DKA(group 1),18 diabetic children with medium metabolic control,whose glycated hemoglobin(HbAlc) below 9%(group 2),22 children with poorly controlled diabetes,whose Hbal c above 9%(group 3),and 36 healthy control children(group 4).Malondialdehyde(MDA),nitrate oxidase(NO),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and metabolic parameters such as fasting blood glucose,HbAlc,blood gas analysis,serum ion,renal function of the subjects were measured.Results Mean serum MDA value was significantly higher in group 1 than in group 2(P ＜0.01) and group 4(P ＜0.01),but was not different from that in group 3 (P ＞0.05).Serum levels of NO were significantly higher in group 1,2 and 3 compared with group 4(P＜0.01).Serum levels of GSH-Px were significantly lower in group 1,2 and 3 than in group 4(P＜0.01).There were no significant differences of serum SOD value among the four groups(P＞0.05).Both serum MDA and NO values in the diabetic patients(groups 1 +2 +3) were positively related to HbAlc(r=0.375,P ＜0.01;r=0.250,P ＜0.05),and serum SOD values in the DKA patients were negatively related to HbAlc(r= -0.507,P＜0.05),there were not any significant relationship between the other oxidative markers and metabolic parameters.Conclusion There is an increase of oxidative stress and decrease of antioxygenic ability in DKA children,and these changes tend to correlate more with markers of diabetic imbalance than with parameters of acute metabolic disturbances of DKA.     

The nitric oxide donor molsidomine prevents ischemia/reperfusion injury of the adult rat small intestine

It is suggested that gastrointestinal mucosal blood flow depends on a balanced release of vasoactive substances from the endothelium. The present study investigated the effects of molsidomine on the small intestine after ischemia-reperfusion (I/R) injury in four groups of 10 rats each composed: (1) SO, sham operation; (2) untreated I/R; (3) ML, I/R plus molsidomine pretreatment; (4) L-NAME, I/R plus N-omega-nitro-L-arginine methyl ester pretreatment. Intestinal ischemia for 45 min and reperfusion for 60 min were applied. Ileum specimens were obtained to determine the tissue level of malondialdehyde (MDA) and histologic changes. Mean MDA levels in the SO, untreated I/R, ML, and L-NAME groups were 95.60 +/- 2.59, 136.90 +/- 4.35, 121.10 +/- 3.38, and 137.40 +/- 4.42 nmol/g wet tissue, respectively. Although the MDA level in the ML group was higher than in the SO group ( P < 0.0001), it was significantly lower compared to the untreated I/R and L-NAME groups ( P < 0.0001, P < 0.0001). Mucosal injury scores (MIS) in groups 1-4 were 0.2 +/- 0.42, 3.9 +/- 0.73, 1.5 +/- 0.70, and 4.1 +/- 0.56, respectively. In group 3 the MIS was significantly lower than in groups 2 and 4 ( P < 0.0001, P < 0.0001). Molsidomine plays a role in attenuating reperfusion injury of the small intestine by depression of tissue MDA levels and MIS and regulates post-ischemic intestinal perfusion while restoring the intestinal microcirculatory blood flow and histologic injury.     

亚细亚酸对兔未成熟肺缺血再灌注损伤的保护作用

目的 观察亚细亚酸对兔未成熟肺缺血再灌注损伤的保护作用。方法 选用15~21日龄新西兰白兔60只,分为5组：假手术组,对照组,亚细亚酸低、中和高剂量组,每组各12只。建立单肺缺血再灌注模型,肺门阻断1 h后,开放再灌注4 h。亚细亚酸低、中和高剂量组分别于术前3 d给予亚细亚酸7.5、15和30 mg·kg-1,假手术组仅开胸不阻断肺门,对照组不予干预。术毕收集肺组织,光镜和电镜观察肺组织病理和超微结构改变。测定肺组织丙二醛（MDA）,细胞毒性活性氧（ROS）-HR、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）水平。Western Blot检测髓样生化因子（MyD）88和核转录因子（NF-κB）水平。ELISA法检测IL-1β、TNF-α水平。结果 ①亚细亚酸中和高剂量组肺缺血再灌注损伤明显减轻,光镜下肺泡与肺泡间隔肿胀程度明显轻于对照组,肺泡腔渗液减少,出血少见。电镜下可见肺泡上皮与血管内皮细胞脱落明显减少。②亚细亚酸中和高剂量组较对照组肺组织MDA,ROS-HR水平明显降低,SOD及GSH-PX水平明显升高;各时点的IL-1β、TNF-α水平也有不同程度下降,特别是再灌注后的2 h和4 h(P<0.05);肺组织中MyD88和NF-κB表达显著下降。③亚细亚酸中和高剂量的保护效果较好。结论 亚细亚酸对未成熟肺缺血再灌注损伤有一定的保护作用,其机制与清除氧自由基和减轻全身炎性反应有关。     

钙敏感受体在大鼠心肌缺血/再灌注损伤中的作用

目的观察钙敏感受体在大鼠心肌缺血/再灌注损伤中的作用及其机制。方法30只Wistar大鼠随机分为3组(每组10只):假手术组(sham组)、缺血/再灌注组(I/R组)和钙敏感受体激动剂组(Gdcl3组),采用冠状动脉结扎和松结的方法,制备大鼠在体心肌缺血/再灌注损伤模型。分别测定血清一氧化氮(NO)、丙二醛(MDA)、超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)水平,光镜及透射电镜下观察心肌结构病理变化。结果I/R组血清LDH、MDA水平明显高于sham组(P<0.01),NO、SOD低于sham组(P<0..01);Gdcl3组血清LDH、MDA水平明显高于I/R组(P<0.01),而NO、SOD低于I/R组(P<0.01)。光镜及透射电镜下可观察到Gdcl3组心肌结构破坏,心肌细胞呈灶状或片状坏死;线粒体损伤,核皱缩,核染色质边集,其病理学改变程度较I/R组严重。结论钙敏感受体激活可使氧自由基产生增加,减少NO含量,降低SOD活性,加重心肌缺血/再灌注损伤。     

光照疗法诱导新生儿氧化应激反应的研究

目的 探讨光照疗法(光疗)对高胆红素血症新生儿氧化应激反应的诱导效应.方法 将60例非溶血性高胆红素血症新生儿随机分为两组:光疗1组30例,入院后持续光疗24 h;光疗2组30例,入院24 h内不予光疗.用比色法测定两组患儿的血清丙二醛(MDA)浓度,血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)性.结果 光疗1组患儿光疗24 h后血清MDA浓度为(18.59±3.11)nmol/ml,明显高于光疗前[(16.13±3.12)nmol/ml],差异有非常显著性(P＜0.01);血清SOD、CAT、GSH-Px活性分别为(63.92±12.40)U/ml、(1.60±0.44)U/ml与(74.33±31.48)酶活力单位,明显低于光疗前[(75.80±13.78)U/ml、(1.87±0.51)U/ml与(90.52±29.88)酶活力单位],差异有非常显著性(P均＜0.01).光疗2组患儿一般治疗24 h后血清MDA浓度,SOD、CAT、GSH-Px活性与治疗前相比,差异无显著性(P均＞0.05).结论 光疗可诱导新生儿氧化应激反应.     

氨力农对大鼠在体肺缺血再灌注损伤的保护作用

目的：探讨氨力农对在体肺缺血再灌注（I/R）损伤的保护作用。方法：夹闭大鼠左肺门1.5 h,再灌注2 h,建立在体缺血再灌注模型。将24只SD大鼠随机分成假手术组,缺血再灌注组（I/R组）和氨力农组（AMR组）,AMR组缺血前30 min给予颈静脉注射氨力农10 mg/kg,再灌注前5 min颈静脉注射氨力农10 mg/kg。再灌注2 h后采颈动脉血检测血气、白细胞介素-1β（IL-1β）、白细胞介素-8(IL-8)、肿瘤坏死因子-α（TNF-α）;摘取左肺测湿干比、超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量并行病理学检查。结果：再灌注2 h后,动脉血氧分压和二氧化碳分压3组间差异无显著性;I/R组肺湿干比和MDA（nmol/mg prot）含量分别为5.3±0.5和0.66±0.16,显著高于假手术组,AMR组上述指标降低至4.8±0.2和0.51±0.09;SOD（U/mg prot）在I/R组为39.3±3.0 ,AMR组为54.7±6.8,较I/R组升高;I/R组血清IL-1β（pg/mL）、IL-8 （pg/mL）、TNF-α(pg/mL)含量分别为22.08±3.85,21.92±5.56,30.50±3.77较假手术组显著升高, AMR组上述指标为16.66±3.02,14.73±2.75和 22.48±3.82,较I/R组低。病理学结果显示：三组动物肺组织结构基本正常,假手术组和AMR组无充血,I/R组充血明显且较其他两组炎症细胞明显增多。结论： 氨力农对肺缺血再灌注损伤具有保护作用,可能与其抗氧化和抑制炎症因子分泌有关。［中国当代儿科杂志,2007,9（3）：233-236］     

Orchiectomy or testosterone receptor blockade reduces intestinal mucosal damage caused by ischemia-reperfusion insult

The aim of the present study was to investigate whether orchiectomy or administration of flutamide an antagonist of the testosterone receptor can reduce oxidative stress and histologic damage in the rat small bowel subjected to mesenteric ischemia/reperfusion (I/R) injury. A total of 32 Sprague-Dawley rats were divided into four groups. Group 1 was control (sham), group 2 was I/R, group 3 was I/R plus orchiectomy (orchiectomy was performed 14 days before I/R), group 4 was I/R plus flutamide (flutamide was given throughout 14 days before mesenteric IR). Rats were subjected to 45 min of mesenteric ischemia followed by 3 h of reperfusion. The levels of ileal malondialdehyde (MDA) and nitric oxide (NO) were found to be significantly lower in orchiectomy and flutamide treatment groups compared with I/R group (P < 0.05). The histopathological injury scores were consistent with the MDA and NO levels. These results suggest that castration or testosterone receptor blockade decreases the level of intestinal I/R injury in male rats and it is an another example for disease variations based on gender differences.     

血栓通注射液对大鼠小肠缺血再灌注损伤的作用

目的采用肠系膜上动脉(SMA)缺血再灌注(I/R)模型,观察血栓通注射液对大鼠小肠I/R损伤的防治作用。方法将30只大鼠随机分为假手术组、I/R组、治疗组。治疗组于SMA再灌注前15分钟静脉注射血栓通注射液,I/R组按同样方式注射生理盐水,假手术组除不夹闭SMA外,其余操作同I/R组。分别观察平均动脉压(MABP)、血浆一氧化氮(NO)、小肠粘膜出血程度、肠组织湿/干重比值、丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性。结果与假手术组比较,I/R组再灌注后60分钟MABP、血浆NO含量显著下降,肠组织湿/干重比值、MDA浓度明显升高(P<0.01),而SOD活性无变化(P>0.05)。治疗组,则能明显减缓这种趋势,各项指标改善,小肠粘膜损伤程度明显减轻(P<0.01)。结论血栓通注射液对大鼠小肠I/R损伤有一定保护作用,其作用机制与抑制脂质过氧化和NO含量增加有关。     

吸入低浓度一氧化氮对胎粪吸入综合征患儿机体抗氧化能力的影响

目的 探讨吸入低浓度一氧化氮(iNO)对胎粪吸入综合征(MAS)患儿机体氧化-抗氧化平衡的影响.方法 将我院新生儿科病房的55例MAS患儿随机分为机械通气+iNO组(A组,n=25)、机械通气组(B组,n=30),并选择我院同期的健康足月新生儿为对照组(C组,n=30).iNO前A、B组均接受气管插管、气管内吸痰、机械通气及静脉滴注抗生素等一般治疗.A组于入院后1～2 h给予iNO治疗,分别在0、24、72 h监测各组患儿静脉血血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、总抗氧化能力(T-AOC)水平.结果 三组患儿一般情况比较差异无显著性.随着NO吸入.A组SOD、T-AOC渐增高,MDA含量降低(P＜0.05).B组SOD在24 h降低,而在72 h呈增高改变,MDA含量变化与之相反,T-AOC呈渐增高改变(P＜0.05).A组机械通气时间及氧暴露时间分别为(77.38±13.97)h与(158.70±47.23)h,明显低于B组[(104.27±10.53)h与(202.15±61.92)h],差异有显著性(P＜0.05),但两组患儿病死率及气漏、肺出血、颅内出血(Ⅱ～Ⅳ级)的发生率差异无显著性(P＞0.05).结论 iNO可减少机械通气及氧暴露时间.MAS患儿体内存在不同程度的氧化-抗氧化失衡,iNO多显示抗氧化活性,有助于机体氧化-抗氧化平衡的调节,对机体具有保护性作用.     

头部亚低温对新生儿缺氧缺血性脑病氧化应激损伤和行为神经评分的影响

目的探讨选择性头部亚低温治疗新生儿缺氧缺血性脑病(HIE)对氧化应激损伤及新生儿行为神经评分(NBNA)的影响。方法选择2010年1～12月入住本院新生儿重症监护病房的中、重度HIE患儿,随机分为亚低温治疗组(观察组)和常规治疗组(对照组),分别检测治疗开始后0h、24h、48h、72h、7天外周血清中超氧化物歧化酶(SOD)和丙二醛(MDA)的浓度,比较两组患儿生后7天、14天及28天的NBNA评分。结果两组患儿治疗开始时SOD浓度和MDA浓度比较差异均无统计学意义(P>0.05)。观察组(28例)在治疗后24h、48h、72h血浆SOD浓度分别为(70.2±10.1)u/ml、(86.8±14.9)u/ml、(108.0±16.9)u/ml,明显高于对照组的(61.5±12.4)u/ml、(65.2±11.0)u/ml、(72.0±13.3)u/ml,血浆MDA浓度分别为(5.23±0.71)mmol/L、(4.40±0.62)mmol/L、(4.28±0.50)mmol/L,明显低于对照组的(6.56±0.70)mmol/L、(7.01±0.67)mmol/L、(6.52±0.66)mmol/L,差异有统计学意义(P均<0.05)。治疗7天两组SOD浓度和MDA浓度比较差异无统计学意义(P>0.05)。生后7天两组患儿NBNA评分比较差异无统计学意义(P>0.05),生后14天、28天观察组NBNA评分明显高于对照组,差异有统计学意义(P<0.05)。结论选择性头部亚低温治疗可通过抑制氧自由基的产生及脂质过氧化物反应,减轻脑缺血再灌注后的氧化应激损伤,起到神经保护作用。