哮喘小鼠模型中內(nèi)質(zhì)網(wǎng)應(yīng)激變化及谷氨酰胺的干預(yù)作用機(jī)制
發(fā)布時(shí)間：2018-09-03 12:03
【摘要】：背景與目的：全世界哮喘發(fā)病率逐漸增加,我國(guó)哮喘患者也逐年上升,因此研究哮喘發(fā)病機(jī)制并尋求有效而副作用小的藥物成為研究熱點(diǎn)。內(nèi)質(zhì)網(wǎng)應(yīng)激(ERS)是真核細(xì)胞的一種保護(hù)性應(yīng)激反應(yīng),病毒感染,氧化應(yīng)激、缺血缺氧、營(yíng)養(yǎng)不足和鈣失衡等均可引起ERS,因此ERS參與多種疾病的病理和生理過(guò)程,包括肝功能損傷,神經(jīng)退行性病變,循環(huán)系統(tǒng)疾病,腫瘤的發(fā)生和發(fā)展等。ERS以多種機(jī)制作用于炎癥反應(yīng)通路,與機(jī)體的炎癥反應(yīng)密切相關(guān),所以ERS也參與了很多炎癥性疾病,呼吸系統(tǒng)疾病中有較多關(guān)于ERS與慢阻肺的關(guān)系報(bào)道,但ERS與哮喘關(guān)系的研究報(bào)道國(guó)內(nèi)甚少,而哮喘本質(zhì)是氣道慢性炎癥,故推測(cè)ERS也參與了哮喘的發(fā)病。哮喘治療目前臨床上主要應(yīng)用激素及支氣管擴(kuò)張藥等,但長(zhǎng)期應(yīng)用可帶來(lái)較多副作用,對(duì)兒童生長(zhǎng)發(fā)育也有一定影響。谷氨酰胺是體內(nèi)非必需氨基酸,主要用做胃粘膜保護(hù)劑治療慢性胃炎,潰瘍等,但也有很多學(xué)者研究發(fā)現(xiàn)谷氨酰胺有抗炎,調(diào)節(jié)免疫,保護(hù)粘膜屏障等作用,而哮喘發(fā)病與T細(xì)胞免疫功能異常有關(guān),而且以慢性氣道炎癥為其特點(diǎn),推測(cè)谷氨酰胺可應(yīng)用于哮喘的治療。本論文主要探討哮喘小鼠模型中內(nèi)質(zhì)網(wǎng)應(yīng)激變化及炎癥因子的改變,并應(yīng)用谷氨酰胺干預(yù)后觀察了谷氨酰胺對(duì)哮喘的治療作用及其可能的作用機(jī)制。 方法： 1.6-8周齡BALB/C小鼠,以卵蛋白及氫氧化鋁致敏后霧化吸入卵蛋白激發(fā)氣道制備哮喘小鼠模型。小鼠隨機(jī)分成5組,每組各10只。A正常對(duì)照組；B哮喘模型組；C低劑量谷氨酰胺治療組：0.4g/kg；D中劑量谷氨酰胺治療組：0.75g/kg；E大劑量谷氨酰胺治療組：1.5g/kg。 2.取各組小鼠血清用ELISA法測(cè)定IL-6,IL-4,IgE,TNF α,IL-12水平； 3.取各組小鼠BALF離心后的細(xì)胞涂片進(jìn)行Diff-quik染色,檢測(cè)白細(xì)胞數(shù)及嗜酸細(xì)胞數(shù)； 4.取各組小鼠BALF上清液用ELISA法測(cè)定IL-6,IL-4。 5.小鼠一側(cè)肺組織甲醛固定后進(jìn)行HE染色觀察肺部炎癥改變。 6.另一側(cè)肺用Western Blot方法檢測(cè)肺組織JNK,pJNK,CHOP,GRP78IRE-1,BAX,Bcl2,Caspase12表達(dá). 7.利用衣霉素制備細(xì)胞ERS模型：體外培養(yǎng)人肺腺癌細(xì)胞株A549細(xì)胞,用MTT法檢測(cè)不同濃度(0.1ug/ml,1ug/ml,10ug/ml)衣霉素對(duì)A549細(xì)胞作用不同時(shí)間(6,12,24,48h)的細(xì)胞增值抑制率,選定應(yīng)用衣霉素合適濃度及時(shí)間。 8.MTT法檢測(cè)不同濃度谷氨酰胺(2,4,8,12,16mmol/1)對(duì)產(chǎn)生內(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng)的A549細(xì)胞的作用不同時(shí)間點(diǎn)(12,24,48小時(shí))的細(xì)胞增殖抑制率,選定應(yīng)用谷氨酰胺的合適濃度及時(shí)間。 9.細(xì)胞培養(yǎng)分5組,空白對(duì)照組：在培養(yǎng)液中只有A549細(xì)胞及；衣霉素組：培養(yǎng)液中加入A549細(xì)胞及衣霉素1ug/ml:不同濃度谷氨酰胺組,分3組：GLN4組：培養(yǎng)液中加入A549細(xì)胞,衣霉素lug/ml以及4mMmmol/1谷氨酰胺；GLN8組：培養(yǎng)液中加入A549細(xì)胞,衣霉素1ug/ml及8mmol/1谷氨酰胺；GLN12組：培養(yǎng)液中加入A549細(xì)胞,衣霉素lug/ml及12mmol/1谷氨酰胺。Western Blot方法檢測(cè)不同細(xì)胞組培養(yǎng)12小時(shí)后的JNNK,pJNK.CHOP,GPR78表達(dá)水平。 結(jié)果： 1.B組(模型組)血清IL-6,IL-4,IgE,TNF α水平較A組(對(duì)照組)明顯升高,IL-12水平明顯降低,差異有顯著性(P0.05)。C,D,E,組血清IL-6,IL-4,IgE,TNF α較B組明顯降低,IL-12水平明顯升高,有統(tǒng)計(jì)學(xué)意義(P0.05)。 2.Diff-quik染色結(jié)果：B組(模型組)肺泡灌洗液中白細(xì)胞數(shù)及嗜酸細(xì)胞計(jì)數(shù)明顯高于A組(正常組)差異有顯著性(p0.05)；C,D,E組肺泡灌洗液中白細(xì)胞數(shù)及嗜酸細(xì)胞數(shù)較模型組明顯減少,但高于正常組,差異有顯著性(P0.05)； 3.B組(模型組)肺泡灌洗液中工L-6,IL-4水平較A組(對(duì)照組)明顯升高,差異有顯著性(P0.05)。C,D,E組肺泡灌洗液中IL-6,IL-4較B組明顯降低,有統(tǒng)計(jì)學(xué)意義(P0.05)。 4.肺組織病理結(jié)果：HE染色結(jié)果,B組與A組比較,支氣管及血管周圍大量淋巴細(xì)胞和嗜酸性粒細(xì)胞等炎性細(xì)胞浸潤(rùn)；支氣管上皮細(xì)胞多處脫落,基底膜可見(jiàn)輕度增厚,支氣管平滑肌有增生表現(xiàn),細(xì)小的支氣管內(nèi)可見(jiàn)到較多粘液栓和炎性滲出物,肺間質(zhì)和肺泡腔內(nèi)也可見(jiàn)炎性細(xì)胞浸潤(rùn)；C.D.E組較模型組比較,支氣管及血管周圍,肺間質(zhì)炎性細(xì)胞浸潤(rùn)明顯減輕,支氣管上皮脫落減少,肺泡腔內(nèi)炎性細(xì)胞減少。 5.B組與A組比較,小鼠肺組織pJNK.CHOP,GPR78,IRE1表達(dá)水平明顯升高,而JNK表達(dá)無(wú)明顯差異,說(shuō)明哮喘發(fā)病時(shí)肺部發(fā)生了內(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng)。谷氨酰胺治療組的pJNK.CHOP,GPR78,IRE1表達(dá)水平較模型組明顯降低,差異有顯著性,說(shuō)明谷氨酰胺對(duì)內(nèi)質(zhì)網(wǎng)應(yīng)激有保護(hù)作用：B組與A組比較,小鼠肺組織BAX/Bcl2,Caspase12表達(dá)水平明顯升高,谷氨酰胺治療組其值降低,說(shuō)明谷氨酰胺通過(guò)抑制內(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng)抑制了細(xì)胞凋亡的發(fā)生： 6.細(xì)胞毒性MTT方法檢測(cè)結(jié)果,衣霉素處理細(xì)胞A549濃度為lug/m1,作用時(shí)間為12小時(shí)時(shí)細(xì)胞增值抑制率為51.3%,最接近50%,故選擇衣霉素作用濃度為lug/ml,作用時(shí)間為12h。 7.MTT法檢測(cè)不同濃度谷氨酰胺(2,4,8,12,16mmol/1)對(duì)產(chǎn)生內(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng)的A549細(xì)胞作用不同時(shí)間點(diǎn)(12,24,48小時(shí))的細(xì)胞增殖抑制率結(jié)果為谷氨酰胺8mmol/l作用12小時(shí)的細(xì)胞增殖抑制率為48.9%,最接近50%,故選擇此濃度及時(shí)間點(diǎn)為合適作用濃度及時(shí)間。 8.體外細(xì)胞培養(yǎng)試驗(yàn)中,衣霉素組較空白對(duì)照組pJNK.CHOP,GPR78表達(dá)水平明顯升高,而JNK表達(dá)無(wú)明顯差異,說(shuō)明衣霉素誘導(dǎo)A549細(xì)胞產(chǎn)生了內(nèi)質(zhì)網(wǎng)應(yīng)激。谷氨酰胺+衣霉素組的pJNK.CHOP,GPR78表達(dá)水平較衣霉素組明顯降低,差異有顯著性,說(shuō)明谷氨酰胺對(duì)內(nèi)質(zhì)網(wǎng)應(yīng)激有保護(hù)作用。 結(jié)論： 1.哮喘時(shí)有IL-4, IL-6, IgE, TNFα這些促炎癥因子水平增高,血清抑炎因子IL-12水平降低；谷氨酰胺治療可降低促炎癥因子的釋放,增加抑炎因子水平,說(shuō)明谷氨酰胺通過(guò)抑制哮喘的炎癥反應(yīng)而起到對(duì)哮喘氣道損傷的保護(hù)作用。 2.哮喘時(shí)肺組織產(chǎn)生了內(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng),并有細(xì)胞凋亡及炎癥的發(fā)生,谷氨酰胺對(duì)內(nèi)質(zhì)網(wǎng)應(yīng)激有保護(hù)作用,并進(jìn)一步抑制了細(xì)胞凋亡及氣道炎癥,從而對(duì)哮喘有治療作用。 3.體外細(xì)胞培養(yǎng)結(jié)果證實(shí),在細(xì)胞水平,谷氨酰胺對(duì)產(chǎn)生內(nèi)質(zhì)網(wǎng)應(yīng)激的A549細(xì)胞有保護(hù)作用。
[Abstract]:BACKGROUND & OBJECTIVE: The incidence of asthma is increasing all over the world, and the incidence of asthma in China is also increasing year by year. Therefore, the study of the pathogenesis of asthma and the search for effective and less side-effect drugs have become a hot spot. Endoplasmic reticulum stress (ERS) is a protective stress response of eukaryotic cells, including viral infection, oxidative stress, ischemia and hypoxia, undernutrition and so on. Calcium imbalance can cause ERS, so ERS is involved in many pathological and physiological processes, including liver function damage, neurodegenerative diseases, circulatory system diseases, tumor occurrence and development. There are many reports about the relationship between ERS and COPD in respiratory diseases, but there are few reports about the relationship between ERS and asthma in China, and the essence of asthma is chronic airway inflammation, so it is speculated that ERS is also involved in the pathogenesis of asthma. Glutamine is a non-essential amino acid in the body, mainly used as a gastric mucosal protective agent in the treatment of chronic gastritis, ulcers, etc., but many scholars have found that glutamine has anti-inflammatory, immune regulation, protection of mucosal barrier and other effects, and the incidence of asthma is related to abnormal T cell immune function, and to Chronic airway inflammation is its characteristic, and glutamine may be used in the treatment of asthma. This paper mainly discusses the changes of endoplasmic reticulum stress and inflammatory factors in asthmatic mice model, and observes the therapeutic effect of glutamine on asthma and its possible mechanism after intervention with glutamine.
Method:
1.6-8 weeks old BALB/C mice were sensitized with ovalbumin and aluminium hydroxide and then inhaled with aerosolized ovalbumin to induce airway asthma in mice. Amido treatment group: 1.5g/kg.
2. serum levels of IL-6, IL-4, IgE, TNF alpha and IL-12 were measured by ELISA in each group of mice.
3. Diff-quik staining was used to detect the number of leukocytes and eosinophils in BALF-centrifuged cells.
4. the supernatants of BALF from each group were determined by ELISA, IL-6, IL-4.
5. one lung tissue of mice was fixed with formaldehyde, then HE staining was used to observe the changes of lung inflammation.
6. on the other side of the lung, the expression of JNK, pJNK, CHOP, GRP78IRE-1, BAX, Bcl2 and Caspase12 in lung tissue were detected by Western Blot.
7. Establishment of cell ERS model with chlamydia: Human lung adenocarcinoma cell line A549 was cultured in vitro. The inhibition rate of proliferation of A549 cells treated with Chlamydia at different concentrations (0.1ug/ml, 1ug/ml, 10ug/ml) for different time (6, 12, 24, 48h) was detected by MTT method.
8. MTT assay was used to detect the inhibitory rate of proliferation of A549 cells at different time points (12,24,48 hours) induced by different concentrations of glutamine (2,4,8,12,16 mmol/1).
9. Cell culture was divided into 5 groups, blank control group: A549 cells and Chlamycin group: A549 cells and Chlamycin 1ug/ml were added into the culture medium, and divided into 3 groups: GLN4 group: A549 cells, Chlamycin lug/ml and 4 mMmmol/1 glutamine were added into the culture medium; GLN8 group: A549 cells were added into the culture medium. GLN12 group: A549 cells were added into the culture medium, and the expressions of JNNK, pJNK.CHOP and GPR78 were detected by Western Blot method 12 hours after culture.
Result:
1. The serum levels of IL-6, IL-4, IgE and TNF-alpha in group B were significantly higher than those in group A (control group), and IL-12 was significantly lower (P 0.05). The serum levels of IL-6, IL-4, IgE and TNF-alpha in group C, D, E were significantly lower than those in group B (P 0.05).
2. Diff-quik staining results: Group B (model group) alveolar lavage fluid white blood cell and eosinophil counts were significantly higher than group A (normal group) difference was significant (p0.05); C, D, E alveolar lavage fluid white blood cell and eosinophil counts were significantly lower than the model group, but higher than the normal group, the difference was significant (P 0.05);
3. The levels of IL-6 and IL-4 in alveolar lavage fluid of group B (model group) were significantly higher than those of group A (control group) (P 0.05). The levels of IL-6 and IL-4 in alveolar lavage fluid of group C, D and E were significantly lower than those of group B (P 0.05).
4. Pulmonary histopathological results: HE staining results, group B and group A compared, bronchial and perivascular lymphocytes and eosinophils infiltration of inflammatory cells; bronchial epithelial cells more exfoliated, basement membrane can be seen slightly thickened, bronchial smooth muscle proliferation, small bronchioles can be seen more mucus thrombus and inflammatory infiltration. Inflammatory cell infiltration was also observed in the pulmonary interstitial and alveolar cavities. Compared with the model group, the infiltration of pulmonary interstitial inflammatory cells was significantly reduced in C.D.E group.
5. Compared with group A, the expression levels of pJNK. CHOP, GPR78 and IRE1 in lung tissues of mice in group B were significantly increased, but the expression of JNK was not significantly different, indicating that the lung had endoplasmic reticulum stress reaction during asthma onset. The expression levels of BAX/Bcl 2 and Caspase 12 in lung tissue of mice in group B were significantly higher than those in group A. The expression levels of BAX/Bcl 2 and Caspase 12 in glutamine treatment group were significantly lower than those in group A.
6. Cytotoxic MTT assay showed that the concentration of Chlamycin treated A549 was lug/m1, and the inhibition rate of cell proliferation was 51.3% at 12 hours, closest to 50%. Therefore, the concentration of Chlamycin was lug/ml and the action time was 12 hours.
7. MTT assay was used to detect the proliferation inhibition rate of A549 cells at different time points (12,24,48 hours) induced by different concentrations of glutamine (2,4,8,12,16 mmol/1). The results showed that the proliferation inhibition rate of A549 cells at different time points (12,24,48 hours) was 48.9% after 12 hours of glutamine 8 mmol/l treatment, which was the closest to 50%. Degree and time.
8. In vitro cell culture test, the expression levels of pJNK. CHOP and GPR78 in the Chlamydia group were significantly higher than those in the blank control group, but there was no significant difference in the expression of JNK, indicating that Chlamydia induced endoplasmic reticulum stress in A549 cells. Amides have protective effects on endoplasmic reticulum stress.
Conclusion:
1. In asthma, the levels of IL-4, IL-6, IgE and TNFalpha increased, while the levels of IL-12 in serum decreased. Glutamine treatment can reduce the release of pro-inflammatory factors and increase the levels of anti-inflammatory factors, indicating that glutamine plays a protective role in airway injury of asthma by inhibiting the inflammatory reaction of asthma.
2. In asthma, endoplasmic reticulum (ER) stress occurs in lung tissues, and there is apoptosis and inflammation. Glutamine has protective effect on ER stress, and further inhibits apoptosis and airway inflammation, thus has therapeutic effect on asthma.
3. Cell culture in vitro showed that glutamine could protect A549 cells from endoplasmic reticulum stress.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R725.6;R-332
本文編號(hào)：2219925
[Abstract]:BACKGROUND & OBJECTIVE: The incidence of asthma is increasing all over the world, and the incidence of asthma in China is also increasing year by year. Therefore, the study of the pathogenesis of asthma and the search for effective and less side-effect drugs have become a hot spot. Endoplasmic reticulum stress (ERS) is a protective stress response of eukaryotic cells, including viral infection, oxidative stress, ischemia and hypoxia, undernutrition and so on. Calcium imbalance can cause ERS, so ERS is involved in many pathological and physiological processes, including liver function damage, neurodegenerative diseases, circulatory system diseases, tumor occurrence and development. There are many reports about the relationship between ERS and COPD in respiratory diseases, but there are few reports about the relationship between ERS and asthma in China, and the essence of asthma is chronic airway inflammation, so it is speculated that ERS is also involved in the pathogenesis of asthma. Glutamine is a non-essential amino acid in the body, mainly used as a gastric mucosal protective agent in the treatment of chronic gastritis, ulcers, etc., but many scholars have found that glutamine has anti-inflammatory, immune regulation, protection of mucosal barrier and other effects, and the incidence of asthma is related to abnormal T cell immune function, and to Chronic airway inflammation is its characteristic, and glutamine may be used in the treatment of asthma. This paper mainly discusses the changes of endoplasmic reticulum stress and inflammatory factors in asthmatic mice model, and observes the therapeutic effect of glutamine on asthma and its possible mechanism after intervention with glutamine.
Method:
1.6-8 weeks old BALB/C mice were sensitized with ovalbumin and aluminium hydroxide and then inhaled with aerosolized ovalbumin to induce airway asthma in mice. Amido treatment group: 1.5g/kg.
2. serum levels of IL-6, IL-4, IgE, TNF alpha and IL-12 were measured by ELISA in each group of mice.
3. Diff-quik staining was used to detect the number of leukocytes and eosinophils in BALF-centrifuged cells.
4. the supernatants of BALF from each group were determined by ELISA, IL-6, IL-4.
5. one lung tissue of mice was fixed with formaldehyde, then HE staining was used to observe the changes of lung inflammation.
6. on the other side of the lung, the expression of JNK, pJNK, CHOP, GRP78IRE-1, BAX, Bcl2 and Caspase12 in lung tissue were detected by Western Blot.
7. Establishment of cell ERS model with chlamydia: Human lung adenocarcinoma cell line A549 was cultured in vitro. The inhibition rate of proliferation of A549 cells treated with Chlamydia at different concentrations (0.1ug/ml, 1ug/ml, 10ug/ml) for different time (6, 12, 24, 48h) was detected by MTT method.
8. MTT assay was used to detect the inhibitory rate of proliferation of A549 cells at different time points (12,24,48 hours) induced by different concentrations of glutamine (2,4,8,12,16 mmol/1).
9. Cell culture was divided into 5 groups, blank control group: A549 cells and Chlamycin group: A549 cells and Chlamycin 1ug/ml were added into the culture medium, and divided into 3 groups: GLN4 group: A549 cells, Chlamycin lug/ml and 4 mMmmol/1 glutamine were added into the culture medium; GLN8 group: A549 cells were added into the culture medium. GLN12 group: A549 cells were added into the culture medium, and the expressions of JNNK, pJNK.CHOP and GPR78 were detected by Western Blot method 12 hours after culture.
Result:
1. The serum levels of IL-6, IL-4, IgE and TNF-alpha in group B were significantly higher than those in group A (control group), and IL-12 was significantly lower (P 0.05). The serum levels of IL-6, IL-4, IgE and TNF-alpha in group C, D, E were significantly lower than those in group B (P 0.05).
2. Diff-quik staining results: Group B (model group) alveolar lavage fluid white blood cell and eosinophil counts were significantly higher than group A (normal group) difference was significant (p0.05); C, D, E alveolar lavage fluid white blood cell and eosinophil counts were significantly lower than the model group, but higher than the normal group, the difference was significant (P 0.05);
3. The levels of IL-6 and IL-4 in alveolar lavage fluid of group B (model group) were significantly higher than those of group A (control group) (P 0.05). The levels of IL-6 and IL-4 in alveolar lavage fluid of group C, D and E were significantly lower than those of group B (P 0.05).
4. Pulmonary histopathological results: HE staining results, group B and group A compared, bronchial and perivascular lymphocytes and eosinophils infiltration of inflammatory cells; bronchial epithelial cells more exfoliated, basement membrane can be seen slightly thickened, bronchial smooth muscle proliferation, small bronchioles can be seen more mucus thrombus and inflammatory infiltration. Inflammatory cell infiltration was also observed in the pulmonary interstitial and alveolar cavities. Compared with the model group, the infiltration of pulmonary interstitial inflammatory cells was significantly reduced in C.D.E group.
5. Compared with group A, the expression levels of pJNK. CHOP, GPR78 and IRE1 in lung tissues of mice in group B were significantly increased, but the expression of JNK was not significantly different, indicating that the lung had endoplasmic reticulum stress reaction during asthma onset. The expression levels of BAX/Bcl 2 and Caspase 12 in lung tissue of mice in group B were significantly higher than those in group A. The expression levels of BAX/Bcl 2 and Caspase 12 in glutamine treatment group were significantly lower than those in group A.
6. Cytotoxic MTT assay showed that the concentration of Chlamycin treated A549 was lug/m1, and the inhibition rate of cell proliferation was 51.3% at 12 hours, closest to 50%. Therefore, the concentration of Chlamycin was lug/ml and the action time was 12 hours.
7. MTT assay was used to detect the proliferation inhibition rate of A549 cells at different time points (12,24,48 hours) induced by different concentrations of glutamine (2,4,8,12,16 mmol/1). The results showed that the proliferation inhibition rate of A549 cells at different time points (12,24,48 hours) was 48.9% after 12 hours of glutamine 8 mmol/l treatment, which was the closest to 50%. Degree and time.
8. In vitro cell culture test, the expression levels of pJNK. CHOP and GPR78 in the Chlamydia group were significantly higher than those in the blank control group, but there was no significant difference in the expression of JNK, indicating that Chlamydia induced endoplasmic reticulum stress in A549 cells. Amides have protective effects on endoplasmic reticulum stress.
Conclusion:
1. In asthma, the levels of IL-4, IL-6, IgE and TNFalpha increased, while the levels of IL-12 in serum decreased. Glutamine treatment can reduce the release of pro-inflammatory factors and increase the levels of anti-inflammatory factors, indicating that glutamine plays a protective role in airway injury of asthma by inhibiting the inflammatory reaction of asthma.
2. In asthma, endoplasmic reticulum (ER) stress occurs in lung tissues, and there is apoptosis and inflammation. Glutamine has protective effect on ER stress, and further inhibits apoptosis and airway inflammation, thus has therapeutic effect on asthma.
3. Cell culture in vitro showed that glutamine could protect A549 cells from endoplasmic reticulum stress.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R725.6;R-332
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 周濟(jì)宏;李幼生;曹亞澄;黎介壽;;腫瘤壞死因子對(duì)谷氨酰胺促大鼠組織蛋白質(zhì)合成的影響[J];腸外與腸內(nèi)營(yíng)養(yǎng);2008年01期
2 周濟(jì)宏;李幼生;洪志堅(jiān);胡心寶;解偉光;黎介壽;;感染狀態(tài)下腫瘤壞死因子和谷氨酰胺的變化[J];腸外與腸內(nèi)營(yíng)養(yǎng);2009年03期
3 全竹富;袁志超;黎介壽;;丙氨酰-谷氨酰胺雙肽對(duì)術(shù)后腸道通透性和全身炎性反應(yīng)的影響[J];腸外與腸內(nèi)營(yíng)養(yǎng);2010年01期
4 安仁哲,Jong-Gyun KIM,Jae-Ho LEE;IL-12對(duì)支氣管哮喘小鼠Th2免疫應(yīng)答的影響[J];中國(guó)當(dāng)代兒科雜志;2005年01期
5 涂海燕;陳新;李靜;;呼吸道合胞病毒感染誘導(dǎo)人支氣管上皮細(xì)胞表達(dá)胸腺基質(zhì)淋巴生成素的信號(hào)轉(zhuǎn)導(dǎo)機(jī)制探討[J];南方醫(yī)科大學(xué)學(xué)報(bào);2007年10期
6 姜莉;張黎川;王琪;王斯炎;;GRP78表達(dá)下調(diào)可降低肺腺癌細(xì)胞對(duì)VP-16的耐藥[J];中國(guó)肺癌雜志;2009年11期
7 張忠彬,夏昭林;內(nèi)質(zhì)網(wǎng)應(yīng)激與疾病[J];國(guó)外醫(yī)學(xué)(衛(wèi)生學(xué)分冊(cè));2003年03期
8 嚴(yán)潔;王秋卉;許紅陽(yáng);戴幼竹;楊挺;;強(qiáng)化谷氨酰胺對(duì)膿毒血癥患者血漿谷胱甘肽濃度的影響[J];廣東醫(yī)學(xué);2013年18期
9 趙莉,麥賢弟,檀衛(wèi)平,黃花榮,黃紹良,朱昌國(guó);哮喘患兒IL-4、IL-12與IgE水平的初步研究[J];臨床兒科雜志;2001年01期
10 徐慧;申昆玲;殷菊;趙宇紅;;IL-12對(duì)小鼠哮喘模型Th亞群和氣道炎癥的影響[J];臨床兒科雜志;2008年09期
，本文編號(hào)：2219925
本文鏈接：http://sikaile.net/yixuelunwen/eklw/2219925.html
最近更新
教材專著
