Anti-inflammatory effect of Mentha longifolia in lipopolysaccharide-stimulated macrophages: Reduction of nitric oxide production through inhibition of inducible nitric oxide synthase

Abstract

Mentha longifolia is an aromatic plant used in flavoring and preserving foods and as an anti-inflammatory folk medicine remedy. The present study assessed the effects of M. longifolia extracts, including essential oil and crude methanol extract and its fractions (ethyl acetate, butanol and hexane), on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression in lipopolysaccharide (LPS)-stimulated J774A.1 cells using real-time polymerase chain reaction (PCR). The cytotoxic effects of the extracts on the cells were examined and non-cytotoxic concentrations (<0.2?mg/ml) were used to examine their effects on NO production and iNOS mRNA expression. Only the hexane fraction that contained high levels of phenolic and flavonoid compounds at concentrations from 0.05–0.20?mg/ml significantly reduced NO production in LPS-stimulated cells (p?<?0.001). Real-time PCR analysis indicated the ability of this fraction at the same concentrations to significantly decrease iNOS as well as TNFα mRNA expression in the cells (p?<?0.001). All extracts were able to scavenge NO radicals in a concentration-dependent manner. At concentrations greater than 0.2?mg/ml, total radicals were 100% scavenged. In conclusion, M. longifolia possibly reduces NO secretion in macrophages by scavenging NO and inhibiting iNOS mRNA expression, and also decreases TNFα pro-inflammatory cytokine expression, thus showing its usefulness in the inflammatory disease process.     

巨噬细胞诱导型一氧化氮合酶的表达调节机制

一氧化氮是一种重要的巨噬细胞免疫效应分子,它参与免疫调节和宿主防御反应.一氧化氮的生成主要由诱导型一氧化氮合酶调节,然而诱导型一氧化氮合酶表达的调节机制及信号通路尚不完全清楚.     

高血压心肌肥厚大鼠心脏组织中高迁移率族蛋白B-1的表达变化

目的 研究高迁移率族蛋白B-1(High mobility group box 1 protein,HMGB1)在心肌肥厚大鼠心肌中的表达变化及意义.方法 利用腹主动脉部分缩窄法在8～10周龄健康成年雄性Wistar大鼠体内构建压力超负荷心肌肥厚模型,并将大鼠随机分成两组:心肌肥厚组(OG)和假手术组(CG).手术后按要求饲养4周后处死,观察离体心脏大小并计算心室重/体重比(mg/g).取部分心肌标本,应用蛋白免疫印迹法(Western Blot)检测心肌组织中HMGB1表达水平.结果 与假手术组相比,心肌肥厚组心肌中HMGB1表达水平显著升高(P＜0.05).结论 压力超负荷可引起心脏组织中HMGB1表达增加及活化,且增加的HMGB1可能参与心肌肥厚的发生和发展过程.     

Local expression of inducible nitric oxide synthase in an animal model of neuropathic pain

Peripheral nerve injury is associated with local inflammation and neuropathic pain. In this study we investigated the local expression of the inducible isoform of nitric oxide synthase (iNOS) following a chronic constriction injury (CCI) to the sciatic nerve, a rat model of neuropathic pain. Western blot analysis and immunohistochemical co-localization methods were used to identify temporal and spatial expression of iNOS and its cells of origin. Changes in mRNA were analyzed by RT-PCR and iNOS specific primers. We report that CCI injury induced local iNOS expression in both macrophages and Schwann cells within and distal to the injury site. The local increase in iNOS mRNA expression paralleled both the temporal and spatial protein expression. This study supports the hypothesis that CCI is associated with a local inflammatory reaction mediated at least in part by iNOS. Local activation of the iNOS-NO system may play an important role in the pathogenesis of peripheral nerve injury and neuropathic pain.     

缺氧诱导因子-1在缺氧诱导一氧化氮合成酶基因表达中的作用

目的 研究缺氧诱导因子-1(HIF-1)在一氧化氮合成酶基因缺氧诱导反应中的作用。方法 体外合成具有HIF-1特异结合位点的DNA片段(红细胞生成素3'-增强子片段),借助脂质体,转入培养的鼠主动脉内皮细胞和肺微血管细胞,用半定量RT-PCR方法测定诱导型一氧化氮合成酶(iNOS)mRNA。结果 (1)大鼠主动脉内皮细胞、肺微血管内皮细胞在常氧下培养,有iNOS基因表达;(2)缺氧能诱导这两种细胞iNOS基因表达增加;(3)野生型EPO3'-增强子片段能阻断缺氧对内皮细胞iNOS基因表达的诱导作用,而突变片段则无此作用。结论 在iNOS基因序列中,可能存在EPO3'-端增强子片段,其参与内皮细胞的缺氧反应。     

高迁移率族蛋白1对内毒素急性肺损伤大鼠中性粒细胞凋亡改变的影响

目的 观察体外高迁移率族蛋白1（HMGB1）对内毒素急性肺损伤（ALI）大鼠中性粒细胞（PMN）凋亡改变的影响，以探讨HMGB1在ALI发病机制中的作用。方法 脂多糖注射复制大鼠急性肺损伤模型，在LPS致伤后不同时相点（有或无正丁酸钠干预时）获取肺组织、外周血中性粒细胞（PMN）、支气管肺泡灌洗液（BALF）。RT-PCR检测肺组织HMGB1 mRNA表达，流式细胞术（FCM）、Giemsa染色及TUNEL法检测PMN的凋亡改变。结果 与对照组比较，LPS急性肺损伤大鼠PMN凋亡率逐渐减低，鼠BALF中PMN凋亡开始时间及无存活细胞时间明显延长；LPS致伤后6-24h肺组织HMGB1 mRNA表达明显增高。正丁酸钠（SB）处理组动物肺组织于伤后6、12h肺组织HMGB1 mRNA表达均显著抑制，与LPS组比较，差异有显著性意义（P〈0．05）；形态学检查显示，LPS致伤后大鼠肺组织出现水肿及明显的病理变化，SB干预可减轻肺损伤的严重程度。致伤后肺损伤程度与肺组织HMGB1表达水平及PMN凋亡改变有关。结论 LPS致伤后，鼠肺HMGB1 mRNA高表达发生较晚，但持续较长时间；SB处理可削弱LPS诱导的PMN凋亡延迟及抑制，下调肺组织HMGB1 mRNA表达。HMGB1可能参与内毒素急性肺损伤时PMN的凋亡延迟及抑制效应。     

Rhodiola sachalinesis induces the expression of inducible nitric oxide synthase gene by murine fetal hepatocytes (BNL CL.2)

We have examined the effect of the aqueous extract of Rhodiola sachalinensis root (RSE), a traditional herbal medicine, on nitric oxide (NO) synthesis in murine fetal hepatocytes (BNL CL.2) by measuring the stable end-product nitrite and the mRNA of inducible NO synthase (iNOS). Interferon-gamma (IFN-γ) by itself failed to induce NO synthesis in BNL CL.2 cells. RSE also did not elicit NO synthesis at concentrations up to 1000 μg/ml, but dose- and time-dependently induced NO synthesis in the presence of IFN-γ in BNL CL.2 cells. Whereas RSE or IFN-γ failed to induce detectable levels of iNOS mRNA, a combination of RSE and IFN-γ markedly induced iNOS mRNA in BNL CL.2 cells. Thus, we found that RSE triggered IFN-γ-primed BNL CL.2 cells to synthesize NO by inducing iNOS gene expression. The capability of RSE to induce NO synthesis might be related to the therapeutic efficacy of RSE on the liver diseases.     

一氧化氮吸入对急性高浓度氧肺损伤新生大鼠肺水通道蛋白1和5表达的影响

目的：观察一氧化氮(NO)吸入对急性高浓度氧肺损伤新生大鼠肺上皮水转运体系的影响。方法：32只新生SD大鼠，随机分为：(1)空气组(C)：予空气48 h；（2）高浓度氧组(O)：予高浓度氧持续吸入48 h，维持FiO₂＞0.95；(3)高浓度氧+NO组(ONO)：予高浓度氧持续吸入48 h，维持FiO₂＞0．95，前24 h同时予1×10-5NO吸入；（4）空气 + NO组(CN)： 予空气48 h，前24 h同时予1×10^-5NO吸入。各组分别测肺组织湿重/干重比值(Q_W/Q_D)，行肺组织病理学检查，用RT-PCR方法测定肺组织AQP1、AQP5、α₁-NKA和α-ENaC mRNA含量。结果： 高浓度氧组肺湿重/干重比值明显高于正常对照组(5.81±1.01 vs 4.33±0.94，P<0.01)；而肺组织AQP1 mRNA含量明显低于正常对照组(0.68±0.38 vs 1.81±0.76， P<0.01)，AQP5mRNA含量无明显变化。1×10^-5 NO+高浓度氧组肺组织湿重/干重比值明显高于高浓度氧组(4.89±0.68 vs 5.81±1.01， P<0.05)；而肺组织AQP1 mRNA含量明显高于高浓度氧组(1.27±0.54 vs 0.68±0.38，P<0.05)，AQP5mRNA含量无明显变化。结论：1×10^-5NO吸入24 h能减轻急性高浓度氧肺损伤新生大鼠的肺水肿，提高肺内水通道蛋白1mRNA含量，水通道蛋白5的mRNA含量无明显改变，提示1×10^-5NO的吸入可能对急性高浓度氧肺损伤新生大鼠肺内水通道蛋白1有一定的保护作用。     

Lack of inducible nitric oxide synthase activity in T cell clones and T lymphocytes from naive and Leishmania major-infected mice

Nitric oxide (NO) generated by the inducible isoform of nitric oxide synthase (iNOS) is implicated in a number of immunological processes including killing of intracellular parasites, suppression of T cell proliferation, production of cytokines and destruction of tissue in autoimmune diseases. Considering that cytokine-activated mouse macrophages, fibroblasts and endothelial cells are potent producers of NO, we investigated whether T cells, as central participants in immune responses, can also be activated for the release of NO. Neither thymocytes nor type 1 or type 2 T helper cell clones generated significant amounts of nitrite (the stable end product of NO in culture supernatants) when stimulated by T cell mitogens, cytokines or antigen in the presence of irradiated antigen-presenting cells. Similarly, T cells freshly isolated from mice acutely infected with the intracellular pathogen Leishmania major did not produce NO upon restimulation in vitro. The lack of NO production was not due to the expression of enzymatically inactive iNOS, as we were unable to detect any iNOS protein in activated T helper clones or in freshly isolated T cells from infected mice by Western (protein) blot analysis. Finally, we tested whether iNOS expression in T cells might be restricted to a minor subpopulation and therefore only detectable on a single cell level. After immunofluorescence staining of lymph node or spleen cells from infected mice with antibodies against iNOS, F4/80- or Thy-1-antigen, macrophages, but no T cells, were found to express iNOS. Thus, we have no evidence that activated T helper cell clones or T cells from L. major-infected mice are high producers of NO.     

The inhibition of retinal inducible nitric oxide synthase overexpression and the attenuation of experimental uveitis by anti-inflammatory drugs in rats

Objective and design:The effect of a steroid and a non-steroid anti-inflammatory drug on the inducible nitric oxide synthase (NOS II) in rats suffering from lipopolysaccharide (LPS)-induced uveoretinitis was studied.Treatments:Rats were injected with LPS to induce uveitis and divided into three groups: treated with LPS only, LPS + dexamethasone and LPS + indomethacin, respectively.Methods:Retinal, peritoneal macrophages and white blood cells were isolated. The activity and the expression of NOS II were followed by citrulline formation and Western blotting, respectively. Phagocytosis of bacteria was also measured.Results:The best induction of NOS II was achieved by the intravitreal administration of LPS. Dexamethasone and indomethacin significantly decreased the activity and the expression of inducible nitric oxide synthase in retinal tissue, peritoneal macrophages and white blood cells. LPS treatment also increased phagocytosis and neither dexamethasone nor indomethacin reversed this effect.Conclusions:The beneficial effects of these drugs in experimental uveitis are mediated, at least partly, by their inhibitory effect on NOS II induction.Received 1 August 2003; returned for revision 4 November 2003; accepted by A. Falus 13 January 2004     

血浆高迁移率族蛋白B1浓度与脑外伤预后的相关性分析

目的：揭示脑外伤患者血浆高迁移率族蛋白B1（HMGBl）浓度,分析其与预后的相关性。方法：收集重型脑外伤患者118例和同期健康体检正常者50例。健康体检正常者静脉血体检时获得,脑外伤患者静脉血在入院时获得。ELISA测定血浆HMGBl浓度,统计分析其与预后的相关性。结果：￡检验显示,脑外伤患者血浆HMGBl浓度（9．4±2．3）ng／ml显著高于健康体检正常者（1．6±0．3）ng／ml（t=9．583,P〈0．01）。多因素分析显示,血浆HMGBI浓度是脑外伤1周内死亡（OR=1．309,95％CI=1．197-1．743,P〈0．01）、1年内死亡（OR=1．476,95％CI=1．208-1．796,P〈0．01）和1年内神经功能预后不良（格拉斯哥预后评分1-3分）（OR=1．419,95％CI=1．218-1．697,P〈0．01）的独立危险因素,ROC曲线分析显示,血浆HMGBl浓度可预测脑外伤1周内死亡（曲线下面积=0．865,95％CI=0．824-0．901,P〈0．01）、1年内死亡（曲线下面积=0．891,95％CI=0．835-0．934,P〈0．01）和1年内神经功能预后不良（曲线下面积=0．876,95％CI=0.832-0．925,P〈0．01）。结论：脑外伤后血浆HMGBl浓度显著升高,临床检测这些指标有助于早期判断脑外伤预后。     

The role of inducible nitric oxide synthase following spinal cord injury in rat

Acute spinal cord injury (SCI) is two-step process that first involves the primary mechanical injury and then the secondary injury is induced by various biochemical reactions. Apoptosis is one of secondary SCI mechanisms and it is thought to play an important role for the delayed neuronal injury. The enhanced formation of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of apoptosis in SCI. The level of .iNOS mRNA peaked at 6 hr after SCI and it declined until 72 hr after SCI in a rat model. Double-immunofluorescence staining revealed that iNOS positive cells were stained for ED-1, synaptophysin, GFAP, and oligodendrocyte marker. The terminal deoxynucleotidyl-transferase-mediated dUDP-biotin nick end-labeling (TUNEL) positive cell count was higher for the 72 hr post-SCI group than for the 24 hr post-SCI group. This cell count was also higher going in the caudal direction than in the rostral direction from the epicenter, and especially for the 72 hr group. Treatment with a selective iNOS inhibitor resulted in the reduction of TUNEL-positive cells at the lesion site. These findings suggest that nitric oxide generated by the iNOS of macrophages, neurons, oligodentrocytes, and astrocytes plays an important role for the acute secondary SCI that results from apoptotic cell death.     

Activation of endothelial nitric oxide synthase following spinal cord injury in mice

Endothelial nitric oxide synthase (eNOS) plays a neuroprotective role after cerebral ischemia through the production of NO, which enhances cerebral blood flow. However, precise details regarding activation of eNOS after spinal cord injury (SCI) largely remain to be elucidated. In the present study we investigated chronological alteration and cellular location of eNOS and phosphorylated (p)-eNOS at Ser(1177) following SCI in mice. Western blot analysis showed eNOS to be significantly phosphorylated at Ser(1177) from 1 to 2 days after mild SCI, with gradual decrease thereafter. Immunohistochemistry revealed the p-eNOS to be mainly expressed in the endothelial cells of microvessels within gray matter under these conditions. These findings suggest that mild SCI activates eNOS in the subacute stage, which increases spinal cord blood flow and may be involved in protective and repair responses.     

L-精氨酸对大鼠脂多糖致急性肺损伤的影响及机理

目的:探讨L-精氨酸对大鼠急性肺损伤的影响及机理.方法:采用尾静脉注射脂多糖(lipopolysaccharide,LPS)制备大鼠急性肺损伤模型.将45只大鼠随机分为三组:生理盐水对照组(NS组)、急性肺损伤模型组(LPS组)和L-精氨酸预处理组(L-Arg组)(n=15),再各分为2、6、24 h三个时间点.LPS组尾静脉注射LPS(6 mg/kg)制备急性肺损伤模型,L-Arg组在造模前0.5 h腹腔注射L-Arg 500 mg/kg.测定各组大鼠不同时间点的动脉血气分析,肺组织湿/干重(W/D)比,肺组织HE病理切片,ELISA法测定血清TNF-α,硝酸还原酶法测定血清NO,Real Time-PCR法测定肺组织iNOSmRNA.结果:LPS组动脉血氧降低、W/D增高、血清TNF-α及NO增高、肺组织iNOSmRNA增高,且与对照组比较有显著差异(P<0.05),肺组织HE病理切片有肺损伤改变.L-Arg组肺损伤有改善,上述检测指标与LPS组有显著差异(P<0.05).结论:L-精氨酸预处理对LPS致大鼠急性肺损伤有保护作用.     

Ulinastatin Preconditioning Attenuates Inflammatory Reaction of Hepatic Ischemia Reperfusion Injury in Rats via High Mobility Group Box 1(HMGB1) Inhibition

Objective It has been found that ulinastatin (UTI) can attenuate hepatic injury in a rat model of ischemia reperfusion (IR), but the specific mechanism is unclear. This study aims to investigate possible pathomechanism of ulinastatin in reducing the inflammatory response after hepatic IR.Methods A male sprague-dawley(SD) rat model of hepatic ischemia reperfusion injury was used. The rats were randomly divided into 4 groups on average, which were 0.9% saline and IR group as control, ulinastatin preconditioning (UPC) group, UPC+rHMGB1 (recombinant HMGB1) group and UPC +anti-HMGB1 group. Serum aminotransferases, TNF-α, IL-1 and Myeloperoxidase (MPO) levels were measured. Histopathology examination and apoptotic cell detection and the different expression of HMGB1 protein were also assessed.Results Serum levels of aminotransferases, cytokines and hepatic MPO in UPC and UPC+anti-HMGB1 groups were significantly lower than those in control group (p<0.05). Decreased histologic damage and apoptosis were also seen in these two groups (p<0.05).Conclusions HMGB1 expressions in UPC and UPC+anti-HMGB1 groups were significantly lower than those in the two control groups (p<0.05), pretreatment with ulinastatin attenuated liver IR injury by reducing HMGB1 expression through its anti-inflammatory effects.     

Effects of HMGB1 on PMN apoptosis during LPS-induced acute lung injury

Objective

To observe the effects of intravenous injection of HMGB1 inhibitor sodium butyrate on changes in apoptosis of PMN during LPS-induced acute lung injury in rats and HMGB1 in vitro on human circulating PMN apoptosis, in order to clarify the role of HMGB1 in the pathogenesis of acute lung injury.

Methods

(1) LPS-induced acute lung injury rat model was developed by LPS infusion. At different time-points after LPS challenge in the presence or absence of sodium butyrate (SB), the rat tissue sample, peripheral blood PMNs and BALF were collected. RT-PCR was applied to examining rat lung tissue HMGB1 mRNA expression level, and Western blotting analysis was adopted to determine expression of rat lung tissue HMGB1 protein. PMN apoptotic changes were determined by flow cytometric (FCM) analysis, Giemsa staining and TdT-mediated dUTP nick end labeling (TUNEL) method. (2) Separated and purified human circulating PMN were coincubated for 24 h with different doses of HMGB1 (0, 10, 100, 1000 ng/ml, respectively) at 37 °C in 5% CO₂. PMN apoptosis rate was determined by flow cytometric (FCM) analysis and by TdT-mediated dUTP nick end labeling (TUNEL) method.

Results

(1) The percentage of apoptosis of PMN in rat model of LPS-induced ALI was gradually decreased as compared with that of normal control. The PMN apoptosis-initiation time and non-survival time in rat BALF prolonged significantly as compared with that of normal control. The injured rat lung tissue HMGB1 mRNA and protein expression was upregulated 6–24 h after LPS exposure; SB intervention significantly ameliorated the upregulation. In addition, the morphologic examination indicated that the edema severity and pathological changes of lung tissues were excessively aggravated in rats after LPS administration. By comparison, SB treatment diminished the severity of lung damage. Combined with lung HMGB1 expression level, the above changes indicate that the pathological changes of lung tissue were related to the injured lung HMGB1 expression, as well as apoptotic changes in PMN. (2) After coincubation of HMGB1 with human circulating PMNs, TUNEL and flow cytometry were performed. The study revealed that PMN apoptosis ratios was (40.53 ± 4.12) % in control group (PMNs + RPMI 1640 medium), (19.05 ± 2.44) % in LPS group (PMNs + RPMI 1640 medium + 10 μg/ml LPS), (40.52 ± 2.73) % in HMGB1-1 group (PMNs + RPMI 1640 medium + 10 ng/ml HMGB1), (34.89 ± 1.15) % in HMGB1-2 group (PMNs + RPMI 1640 medium + 100 ng/ml HMGB1), and (18.77 ± 3.02) % in HMGB1-3 group (PMNs + RPMI 1640 medium + 1 000 ng/ml HMGB1). There was statistical significance. Meanwhile, PMN TUNEL positive rate was (31.42 ± 4.40) %, (31.39 ± 3.80) %, (25.62 ± 2.46) %, and (17.98 ± 3.20) % in control group, HMGB1-1 group, HMGB1-2 group and HMGB1-3 group, respectively. The inhibitory effect was HMGB1 dose-depended as compared with that of control group.

Conclusion

After LPS challenge, high expression of rats' lung HMGB1 mRNA occurs at a later phase, but keeps for a long time. Sodium butyrate (SB) treatment attenuated LPS-induced PMN apoptosis delay and inhibition, and down-regulated HMGB1 mRNA expression of injured lung. HMGB1 in vitro inhibited human circulating PMN apoptosis markedly, and the inhibitory effect was HMGB1 dose-depended. The results demonstrated that HMGB1 may play an important role as a modulator in apoptotic changes in PMN during LPS-induced ALI. It concludes that HMGB1 may contribute to the development of PMN apoptotic changes during LPS-induced acute lung injury.     

Expression of inducible nitric oxide synthase in macrophages and smooth muscle cells in various types of human atherosclerotic lesions

 Nitric oxide (NO) is an important regulatory agent in blood vessels. We studied the expression of inducible nitric oxide synthase (iNOS) in different types of human atherosclerotic lesions using simultaneous in situ hybridization and immunocytochemistry. Since nitric oxide and its derivates or reaction products can have both oxidative and antioxidative effects, we also studied the presence of oxidized low-density lipoproteins (ox-LDL) and peroxynitrite-modified proteins in the same lesions as indicators of oxidative damage. Twenty-seven aortic samples were studied from seven autopsies. Samples were classified microscopically as normal areas, initial lesions (type I), fatty streaks (type II), intermediate lesions (type III), atheroma (type IV), fibroatheroma lesions (type Va) and fibrotic lesions (type Vc). In normal arterial wall iNOS mRNA was expressed at a low level in smooth muscle cells (SMCs). Absence of, or a low level of, epitopes characteristic of ox-LDL was found in the normal arterial wall. The expression of iNOS mRNA and protein was induced in macrophages and SMCs in the majority of early lesions and in all advanced atherosclerotic lesions. Epitopes characteristic of ox-LDL and peroxynitrite-modified proteins tended to be colocalized in iNOS-positive lesions. We consider that iNOS and oxidative injuries may play an important part in atherogenesis. Received: 24 November 1998 / Accepted: 2 February 1999     

单羧酸转运蛋白1在低糖条件下促进M1型小胶质细胞中诱导型一氧化氮合酶表达

目的 探讨在缺血环境下诱导型一氧化氮合酶(iNOS)和单羧酸转运蛋白1(MCT1)与M1型 促炎性小胶质细胞的关系。 方法 小鼠6只,采用光化学栓塞法制作脑缺血模型;BV2细胞使用含5mmol/L低糖培养基刺激2h。 使用免疫荧光染色、Western blotting方法检测缺血小鼠大脑中小胶质细胞和低糖刺激的BV2细胞中iNOS、MCT1及精氨酸酶1(ARG1)的表达。用RNA干扰及质粒转染技术分别调控未处理BV2细胞中的MCT1表达,检测iNOS及ARG1的变化。 结果 激光制作脑缺血模型成功后,缺血侧半球中iNOS和MCT1以及ARG1的表达升高（P<0.01）,且MCT1主要表达在离子钙接头蛋白分子1（Iba1）阳性和iNOS阳性的小胶质细胞中。低糖刺激BV2小胶质细胞后,iNOS和MCT1表达升高（P<0.001）,而ARG1表达降低（P<0.01）,MCT1主要表达在iNOS阳性的BV2细胞中。RNA干扰BV2细胞后,细胞中MCT1表达降低,iNOS表达下降（P<0.01）;质粒转染BV2细胞后,MCT1表达增高,iNOS表达增加（P<0.01）。但在两种情况下,ARG1表达水平均未发生明显变化。 结论 在低糖环境中小胶质细胞向M1表型极化,MCT1和iNOS表达同时增高,MCT1参与iNOS的表达上调,可能处于iNOS调节通路的上游。