The role of interleukin-13 in the removal of hyper-radiosensitivity by priming irradiation

It has previously been demonstrated that the presence of fetal bovine serum is necessary for TGF-β3 (transforming growth factor beta 3)-dependent elimination of low-dose hyper-radiosensitivity (HRS) in cells by 1 h of low-dose-rate γ-irradiation (0.2–0.3 Gy/h). The purpose of the present study was to identify the serum constituent involved. Two human HRS-positive (T-47D, T98G) cell lines were used. The effects of different pretreatments on HRS were investigated using the colony assay. Total inducible nitric oxide synthase (iNOS) levels were measured using a cell-based ELISA assay. The serum factor was identified as interleukin-13 (IL-13). In order for low dose-rate irradiation to eliminate HRS through the TGF-β3-dependent mechanism, the cells must be exposed to IL-13 first. Inhibiting receptor IL-13Rα2 showed that this receptor is involved in the response. Adding IL-13 to serum-free medium restored the properties of full medium but not when an inhibitor of proprotein convertase activity was added together with IL-13. The presence of IL-13 resulted in upregulation of total iNOS protein levels. Thus, this study indicates that IL-13 interacts with the cells though receptor IL-13Rα2 and induces upregulation of iNOS and activation of one or more furin-like proprotein convertases.     

增强型体外反搏对心脏骤停犬血清一氧化氮系统的影响

目的观察探讨增强型体外反搏(EECP)对心脏骤停(CA)犬血清一氧化氮系统的影响。 方法将16只雄性杂种犬(体重10～15 kg,犬龄18～30个月)根据随机数字表法随机分为EECP组和对照组,每组8只。采用心外膜电致颤诱发CA,经心肺复苏(CPR)至自主循环恢复(ROSC)后,EECP组行连续EECP干预3 h,对照组不予EECP干预。于自主循环恢复(ROSC)后15 min、4 h和96 h采静脉血,用酶联免疫吸附剂测定(ELISA)法测血清一氧化氮(NO)、内皮型一氧化氮合酶(eNOS)、神经元型一氧化氮合酶(nNOS)、诱导型一氧化氮合酶(iNOS)的浓度变化。 结果EECP组在ROSC后4 h、96 h的血清NO、eNOS浓度高于对照组[ROSC后4 h：(34.41±10.01) nmol/ mL>(19.65±5.84) nmol/ mL,(63.86±17.54 ) nmol/mL>(41.01±8.86) nmol/mL,P<0.01;ROSC后96 h：(40.64±12.94) nmol/ mL>(25.80±6.04) nmol/ mL,(47.43±19.40) nmol/ mL>(27.73±11.41) nmol/ mL,P<0.05]; EECP组在ROSC后4 h、96 h的血清iNOS浓度分别为(73.11±32.82) U/ mL和(56.36±33.30) U/ mL,低于对照组的(129.88±45.49) U/ mL和(110.38±53.69) U/ mL(P均<0.05)。 结论EECP可升高CA-ROSC犬血清NO浓度,可能与上调血清eNOS水平并下调血清iNOS水平有关,利于CA后脑复苏。     

No induction of p53 phosphorylation and few focus formation of phosphorylated H2AX suggest efficient repair of DNA damage during chronic low-dose-rate irradiation in human cells

Human fibroblast cells obtained from a normal individual and immortalized by introduction of the hTERT gene were irradiated with 0 to 5 Gy of acute high-dose-rate radiation (1.8 Gy/min) or chronic low-dose-rate radiation (0.3 mGy/min) in the G0 phase, and p53 activation was studied. After high-dose-rate irradiation, a dose-dependent induction of Ser15 phosphorylation was observed, whereas after low-dose-rate irradiation almost none was observed. Then we analyzed the focus formation of phosphorylated histone H2AX protein, which is closely correlated with the induction of double-strand breaks. High-dose-rate radiation induced a significant number of foci in a dose-dependent manner, whereas, low-dose-rate radiation could induce only a few foci even at the highest dose. These results strongly suggest that DNA damage induced by low-dose-rate radiation such as a double-strand break is efficiently repaired during chronic irradiation.     

三氯乙烯对肝细胞一氧化氮和诱导型一氧化氮合酶表达水平的影响

[目的]研究三氯乙烯（TCE）染毒对L-02肝细胞一氧化氮（NO）合成和诱导型一氧化氮合酶（iNOS）表达水平的影响。[方法]用TCE不同浓度（0、0.125、0.25、0.5、1.0、2.0mmol／L）和1.0mmol／LTCE不同染毒时间（0、1、2、6、12、24h）染毒肝细胞。按试剂盒说明检测细胞培养液中NO浓度;提取肝细胞RNA,用荧光定量聚合酶链式反应（PCR）检测肝细胞iNOS mRNA相对表达量。用全自动生化分析仪测定TCE染毒肝细胞后培养液中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）活性。[结果]不同浓度TCE染毒肝细胞24h后,各染毒组和对照组比较,NO和iNOS mRNA表达水平均明显升高;用同一浓度TCE（1.0mmol／L）染毒不同时间,≥2h染毒时间引起NO合成和iNOS mRNA表达水平升高。TCE各剂量组染毒后ALT、AST和LDH高于对照组。[结论]TCE染毒肝细胞可诱导肝细胞iNOS mRNA表达水平升高和NO合成增加,并对肝细胞有一定的损伤作用,提示TCE的肝细胞损害作用可能与NO产生有关。     

Involvement of inducible nitric oxide synthase in radiation-induced vascular endothelial damage

The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-N^ω-nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N⁶-(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage.     

牛磺酸对糖尿病大鼠视网膜NO及其合酶影响

目的 探讨牛磺酸对糖尿病大鼠视网膜一氧化氮(NO)及其合酶(NOS)表达的影响.方法 链脲佐菌素制备大鼠糖尿病模型,24只成年雄性SD大鼠随机分成对照组、糖尿病组、牛磺酸干预组,每组8只.牛磺酸干预组饲料添加1.2%牛磺酸.12周处死,取视网膜标本进行实验.硝酸还原酶测定NO含量,免疫组化法测定神经型一氧化氮合酶(nNOS)及诱导型一氧化氮合酶(iNOS)的表达.结果 糖尿病组与牛磺酸干预组NO含量表达为(2.138±0.260)和(1.053±0.159)μmol/L,差异有统计学意义(P<0.01);糖尿病组与牛磺酸干预组iNOS吸光度分别为(0.390±0.022)和(1.101±0.006),后者明显低于前者(P<0.01);牛磺酸干预组nNOS吸光度为(0.429±0.035),明显高于糖尿病组的(0.125±0.024)(P<0.01).结论 牛磺酸通过减少视网膜NO含量和影响iNOS、nNOS表达,改变糖尿病性视网膜病变(DR).     

维生素C对镍诱导的肺泡巨噬细胞氧化损伤的保护作用

目的:研究维生素C(VC)拮抗Ni2O3的细胞氧化损伤的作用及对大鼠肺泡巨噬细胞iNOS诱导表达的影响。方法:采用体外细胞培养法测定在VC(25,50,100μmol/L)作用下,体外染镍肺泡巨噬细胞的死亡率及活力。同时观察细胞内丙二醛(MDA)、一氧化氮(nitricoxide,NO)和活性氧(ROS)的产生;超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、诱导型一氧化氮合酶(nitricoxidesynthase,iNOS)活力的变化以及应用RT-PCR法测定iNOSmRNA的表达。结果:在体外染镍肺泡巨噬细胞中加入不同浓度的VC后可降低该细胞的死亡率并提高细胞的活力,可减少MDA、NO和活性氧的产生,降低NOS的活性,提高SOD、GSH-Px、CAT的活性,iNOSmRNA表达也较镍组降低。结论:镍可致细胞脂质过氧化,VC可通过提高抗氧化酶的活性,抑制iNOSmRNA的表达,减少活性氧及NO的产生,拮抗镍对肺泡巨噬细胞的氧化损伤。     

大鼠心肌缺血再灌注IL-10、NOS、iNOS的变化

目的探讨缺血再灌注中白介素10（IL—10）、总一氧化氮合酶（NOS）及诱导型一氧化氮合酶（iNOS）变化及关系，为，临床诊治缺血再灌注损伤提供实验依据。方法将大鼠随机分成缺血／再灌注（对照组）、甲基强的松龙治疗组（药物组）2组，在心肌缺血前用甲基强的松龙（30mg／kg）对药物组大鼠预处理，分别测定缺血0．5h、再灌注0.5h及2h血清IL-10、NOS、iNOS。结果对照组与药物组自缺血0．5h、再灌注0．5h至2h IL-10、NOS、iNOS呈逐渐升高趋势，具有显著性差异（P〈0．01），各时段内，药物组较对照组IL—10明显升高，差异有统计学意义（P〈0．01—0.05）；再灌注后药物组NOS，iNOS较对照组降低，差异有统计学意义（P〈0．01—0．05）。IL—10分别与NOS、iNOS呈显著负相关（NOS：r=-0．830，P〈0.01；iNOS：r=-0.788，P〈0．01）。结论在大鼠心肌缺血再灌注中，甲基强的松龙可促进内源性IL—10大量释放；IL-10通过抑制NOS、iNOS的产生抑制炎症反应，减少心肌缺血再灌注损伤，发挥保护作用。     

Ionizing radiation alters organoid forming potential and replenishment rate in a dose/dose-rate dependent manner

Intestinal organoids are an in vitro cultured tissue model generated from intestinal stem cells, and they contain a mixture of epithelial cell types. We previously established an efficient ‘one cell/well’ sorting method, and defined organoid-forming potential (OFP) as a useful index to evaluate the stemness of individual cells. In this study, we assessed the response to radiation dose and dose-rate by measuring both OFP and the percentage of stem cells in the crypts. After high-dose-rate (HDR, 0.5 Gy/min) irradiation in vivo, the percentage of stem cells in the harvested crypt cells decreased, and the replenishment of cycling stem cells originating from dormant cells was enhanced, but OFP increased in cells irradiated with a total dose of >1 Gy. In contrast, at a total dose of 0.1 Gy the percentage of stem cells reduced slightly, but neither replenishment rate nor OFP changed. Furthermore, the response to 1 Gy of low-dose-rate (LDR) irradiation was similar to the response to 0.1 Gy HDR irradiation. These results suggest that 0.1 Gy HDR irradiation or 1 Gy LDR irradiation does not alter stemness. Additionally, the OFP increase in the colon in response to irradiation was smaller than that in the duodenum, similar to the percentage of stem cells. Understanding the differences in the response of stem cells between the colon and the duodenum to radiation is important to clarify the mechanisms underlying the development of radiation-associated intestinal cancers.     

妊娠肝内胆汁淤积症孕妇血清和脐血清NO变化及胎盘NOS的表达

目的:通过测定妊娠肝内胆汁淤积症(ICP)患者血清、脐血清一氧化氮(NO)水平及胎盘一氧化氮合酶(NOS)的表达强度,探讨NO在ICP围产儿不良结局中的作用。方法:以ICP孕妇31例为ICP组,正常孕妇30例为对照组,采用亚硝酸盐法测定母血、脐血NO水平,免疫组化检测胎盘iNOS和eNOS表达强度,对染色强度进行图像分析。结果:ICP组脐血NO水平低于对照组(P<0.01),胎盘iNOS和eNOS表达强度均显著低于对照组(分别为P<0.001和P<0.01),两组孕妇血清NO水平无显著差异(P>0.05)。结论:ICP患者胎盘绒毛组织iNOS和eNOS表达降低,可能导致胎儿-胎盘循环阻力升高,是ICP患者发生胎儿宫内窘迫和早产的原因之一。     

一氧化氮系统与高血压

生物信息分子一氧化氮（Nitric oxide，NO）兼有信息物质与神经递质的功能，参与多种细胞生理活动。一氧化氮在心血管疾病中发挥了重要作用，一氧化氮是在一氧化氮合酶（NOS）催化下生成的。三种不同的NON在心血管疾病中的作用各不相同，一氧化氮合酶／一氧化氮系统在高血压发生及发展中起重要作用。     

Prednisolone inhibits SaOS2 osteosarcoma cell proliferation by activating inducible nitric oxide synthase

AIM: To investigate the effect of prednisolone, a synthetic glucocorticoid used in inflammatory diseases, on the growth of cultured osteosarcoma cells. METHODS: Two osteosarcoma cell lines with different degree of differentiation were used. SaOS2 show a rather mature phenotype, while U2OS are negative for almost all osteoblastic markers. The cells were exposed to different concentrations of prednisolone (1-9 μmol/L) with or without antioxidants or the inhibitor of inducible nitric oxide synthase (iNOS) l-N⁶-(iminoethyl)-lysine-HCl (L-NIL). Cell growth was assessed by counting viable cells. The production of nitric oxide (NO) was measured in the conditioned media by the Griess method. The production of reactive oxygen species was quantified using 2’-7’-dichlorofluorescein diacetate. Western blot with specific antibodies against NOSs was performed on cell extracts. RESULTS: Prednisolone inhibited SaOS2 cell growth in a dose dependent manner. No significant effects were observed in U2OS. The inhibition of SaOS2 growth is not due to oxidative stress, because antioxidants do not rescue cell proliferation. Since high concentrations of NO inhibit bone formation, we also measured NO and found it induced in SaOS2, but not in U2OS, exposed to prednisolone, because of the upregulation of iNOS as detected by western blot. Therefore, we treated SaOS2 with prednisolone in the presence or in the absence of L-NIL. L-NIL prevented NO release induced by prednisolone at all the concentrations apart from 9 μmol/L. At the same concentrations, we found that L-NIL rescued SaOS2 growth after exposure to prednisolone. In U2OS cells, prednisolone did not induce NO production nor affected cell growth. All together, these data indicate that a link exists between increased amounts of NO and growth inhibition in response to prednisolone in SaOS2. CONCLUSION: Prednisolone inhibited SaOS2 proliferation by increasing the release of NO through the upregulation of iNOS, while no effect was exerted on U2OS.     

花色苷对脂多糖诱导巨噬细胞炎症反应的影响

目的探讨花色苷对脂多糖(LPS)所诱导的THP-1样巨噬细胞中诱导性一氧化氮合酶(iNOS),环氧合酶-2(COX-2)及其产物一氧化氮(NO),前列腺素E2(PGE2)表达的影响。方法THP-1单核细胞用终浓度为167nmol/L的佛波酯(PMA)刺激48h诱导成THP-1样巨噬细胞后,分别用1、10、50、100μmol/L的花色苷标准品矢车菊素-3-葡萄糖苷(Cy-3-g)或芍药素-3-葡萄糖苷(Pn-3-g)孵育细胞2h,再用1μg/mlLPS处理细胞12h,用半定量RT-PCR法分别检测iNOS、COX-2的基因表达量,用Western blotting检测iNOS、COX-2的蛋白表达量,分别用Griess法和碱性磷酸酶法(EIA)检测THP-1样巨噬细胞培养基中NO及PGE2的含量。结果花色苷能有效的下调iNOS,COX-2的基因及蛋白水平,且其所合成的炎性介质NO和PGE2也显著降低。结论花色苷能够降低LPS所诱导的THP-1样巨噬细胞中iNOS,COX-2及其产物NO,PGE2的表达水平,提示其可能对于治疗各种炎症相关性疾病如动脉粥样硬化等有着重要的意义。     

叶黄素对D-半乳糖致氧化损伤小鼠HO-1、TLR4表达的影响

目的研究叶黄素缓解D-半乳糖诱导小鼠氧化应激损伤的作用机制。方法 48只昆明种小鼠随机分为D-半乳糖模型对照组、叶黄素低剂量组(10mg/kg·d)、叶黄素高剂量组(40mg/kg·d)和正常对照组。6周后观察小鼠肝组织活性氧(ROS)、一氧化氮(NO)含量,总一氧化氮合酶(TNOS)、诱导型一氧化氮合酶(iNOS)和线粒体ATP酶(ATPase)活性,RT-PCR法检测血红素氧合酶(HO-1)和toll样受体4(TLR4)mRNA表达水平。结果叶黄素低、高剂量组小鼠肝组织ROS含量低于模型对照组(P0.01);低、高剂量组线粒体Na+-K+-ATP酶及高剂量组线粒体Ca2+-ATP酶活性高于模型对照组(P0.05);高剂量组TNOS、iNOS活性及NO含量低于模型对照组(P0.05);高剂量组小鼠肝HO-1mRNA表达高于模型对照组(P0.05),叶黄素低、高剂量组TLR4mRNA表达均低于模型对照组(P0.01)。结论叶黄素降低D-半乳糖小鼠氧化应激效应可能与其提高HO-1表达和下调TLR4mRNA表达有关。     

Induction of rhodanese, a detoxification enzyme, in livers from mice after long-term irradiation with low-dose-rate gamma-rays

The health effects of low-dose radiation exposure are of public concern. Although molecular events in the cellular response to high-dose-rate radiation exposure have been fully investigated, effects of long-term exposure to extremely low-dose-rate radiation remain unclear. Protein expression was analyzed by two-dimensional electrophoresis in livers from mice irradiated for 485 days (22 hr/day) at low-dose-rates of 0.032 microGy/min, 0.65 microGy/min and 13 microGy/min (total doses of 21 mGy, 420 mGy and 8000 mGy, respectively). One of the proteins that showed marked changes in expression was identified as rhodanese (thiosulfate sulfurtransferase). Rhodanese expression was increased after irradiation at 0.65 microGy/min and 13 microGy/min, while its expression was not changed at 0.032 microGy/min. Rhodanese is a detoxification enzyme, probably related to the regulation of antioxidative function. However, antioxidative proteins, such as superoxide dismutase (SOD)1 (also known as Cu,Zn-SOD) and SOD2 (also known as Mn-SOD), which can be induced by high-dose-rate radiation, were not induced at any low-dose-rates tested. These findings indicate that rhodanese is a novel protein induced by low-dose-rate radiation, and further analysis could provide insight into the effects of extremely low-dose-rate radiation exposure.     

Arginine Supplementation Induces Arginase Activity and Inhibits TNF‐α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction

Background: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor–α (TNF‐α) and interleukin‐10 (IL‐10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals. Material and Methods: Male C57BL6/J wild‐type (WT) and iNOS knockout (iNOS–/–) mice were randomized into 6 groups: Sham and Sham–/– (standard chow), IO and IO–/– (standard chow + IO), and Arg and Arg–/– (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF‐α and IL‐10 levels were analyzed in splenic macrophage cultures. Results: Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO–/–, and Arg–/– groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF‐α levels (Arg vs IO group, P < .05) and maintenance of IL‐10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham–/–, IO–/–, and Arg–/– vs other, P < .05). Conclusions: Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF‐α levels, which may be directly related to nitric oxide derived from arginine.     

燃煤污染型氟中毒大鼠脑组织NOS活性及NO含量改变

目的 探讨燃煤型氟中毒对大鼠脑组织一氧化氮合酶（NOS）活性及一氧化氮（NO）含量影响。方法 24只SD大鼠随机分为3组,对照组、低、高氟组。染氟组以地氟病区燃煤烘烤的玉米为主要饲料,复制氟中毒动物模型,6个月后用氟离子选择电极法检测动物尿及脑氟含量,比色法测定脑组织NOS活性,硝酸还原酶法测定脑组织NO含量。结果 染氟6个月时,低、高氟组大鼠尿氟为（2.87±0.12）、（5.27±0.15）mg/L,脑氟为（1.14±0.04）、（1.79±0.04）mg/kg,明显高于对照组[尿氟（1.68±0.02）mg/L,脑氟（0.52±0.05）mg/kg],差异有统计学意义（P<0.05）;低氟组大鼠脑组织白细胞/巨噬细胞性NOS（iNOS）活性[（8.04±3.90）kU/g]与低、高氟组大鼠脑组织中NO含量[分别为（3.13±0.63）、（4.25±0.66）μmol/L]明显高于对照组[iNOS活性（4.02±0.20）kU/g、NO含量（2.29±0.46）μmol/L],差异有统计学意义（P<0.05）。结论 饲喂燃煤型氟中毒病区燃煤烘烤的饲料可致大鼠氟中毒,导致大鼠脑组织中iNOS活性及NO含量升高。     

Protective role of oligonol from oxidative stress-induced inflammation in C6 glial cell

BACKGROUND/OBJECTIVES

Natural products or active components with a protective effect against oxidative stress have attracted significant attention for prevention and treatment of degenerative disease. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from Litchi chinensis Sonn. We investigated the protective effect and its related mechanism of oligonol against oxidative stress.

MATERIALS/METHODS

Oxidative stress in C6 glial cells was induced by hydrogen peroxide (H₂O₂) and the protective effects of oligonol on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) synthesis, and mRNA expression related to oxidative stress were determined.

RESULTS

Treatment with oligonol inhibited NO and ROS formation under cellular oxidative stress in C6 glial cells. In addition, it recovered cell viability in a dose dependent-manner. Treatment with oligonol also resulted in down-regulated mRNA expression related to oxidative stress, nuclear factor kappa-B (NF-κB) p65, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the control group treated with H₂O₂. In particular, expression of NF-κB p65, COX-2, and iNOS was effectively reduced to the normal level by treatment with 10 µg/mL and 25 µg/mL of oligonol.

CONCLUSIONS

These results indicate that oligonol has protective activity against oxidative stress-induced inflammation. Oligonol might be a promising agent for treatment of degenerative diseases through inhibition of ROS formation and NF-κB pathway gene expression.     

脑白质损伤新生大鼠VEGF及iNOS表达变化研究

目的 研究缺氧缺血(HI)对新生大鼠脑白质细胞血管内皮生长因子(VEGF)及诱导型一氧化氮合酶(iNOS)表达的影响,探讨VEGF及iNOS在新生大鼠脑白质损伤(WMD)发病机制中的作用。方法 将3日龄大鼠随机分为实验组及假手术组,建立新生大鼠WMD模型,分别予HI后12、24、48、72 h及7 d处死,对其脑组织取材后行HE染色观察其病理改变,并应用免疫组织化学法检测其VEGF及iNOS的表达水平。结果 在新生大鼠脑白质中,1)VEGF表达水平予HI后12 h开始明显上升,24 h后达高峰,至7 d恢复正常,与对照组比较,实验组脑室周围白质VEGF的表达在12、24、48、72 h有统计学意义。2)实验组iNOS于HI后12 h表达开始增加,72 h达高峰,7 d仍有表达,与对照组比较,差异有统计学意义。 结论 HI可导致新生大鼠脑白质VEGF及iNOS的表达水平显著增高,参与新生大鼠WMD的病理生理过程。