褪黑素对LPS致大鼠海马炎性损伤的保护作用

doi:10.11843/j.issn.0366-6964.2021.024

Abstract

Abstract: The purpose of this study was to explore the protective effect of melatonin (MT) on hippocampal inflammatory injury induced by lipopolysaccharide (LPS) in rats. Forty 4-week-old healthy male SD rats were randomly divided into 4 groups:control group (CON group), model group (LPS group), MT intervention group (LPS+MT group) and MT group. Four hours after intraperitoneal injection of 10 mg·kg^-1 MT and/or 10 mg·kg^-1 LPS, the behavior of rats was tested by open field test. The hippocampus was weighed and coefficient of hippocampus was calculated. The pathological changes of the hippocampal region of brain were observed by hematoxylin-eosin (HE) staining. The mRNA expressions of microglial activation markers Iba-1 and CD11b in hippocampus were detected by RT-PCR. The protein expressions of inflammatory cytokines IL-1β, TNF-α, IL-6, IL-10 and TGF-β in hippocampus were detected by Weston blot. The results showed that compared with CON group, the autonomous exploration behavior and motor ability of rats in LPS group were decreased; the arrangement of nerve cells in hippocampus was loose, and the intercellular space of hippocampus was enlarged, cytoplasmic pyknosis was deeply stained, glial cells were infiltrated; the expression of microglia activation markers Iba-1 and CD11b mRNA were significantly increased (P<0.01); the protein expressions of pro-inflammatory factors IL-1β, TNF-α and IL-6 were significantly increased in LPS group (P<0.01); the protein expression of anti-inflammatory factors IL-10 and TGF-β decreased significantly (P<0.01). Compared with LPS group, the autonomous exploration behavior and motor ability of rats in LPS+MT group were increased; the arrangement of nerve cells in hippocampus was compact, and there was no obvious pathological change; the mRNA expressions of microglia activation markers Iba-1 and CD11b were significantly decreased (P<0.01); the protein expressions of pro-inflammatory factors IL-1β, TNF-α and IL-6 were significantly decreased in LPS+MT group (P<0.01); the protein expression of anti-inflammatory factors IL-10 and TGF-β increased significantly (P<0.1). In addition, there was no significant difference in all indexes between MT group and CON group (P>0.05). The above results suggest that MT can inhibit the activation of microglia and reduce the inflammatory response of hippocampus, thus improving the inflammatory injury of hippocampus induced by LPS in rats.

Key words: melatonin, LPS, hippocampal inflammation, microglia, sepsis, rat

CLC Number:

S857.11

ZHANG Haiyang, LU Xiangyu, ZHANG Jiahua, LIU Xin, HAN Zhengxuan, CUI An, ZHAO Yuan, SONG Manyu, LIU Tao, FAN Honggang. Protective Effects of Melatonin on LPS-induced Hippocampal Inflammatory Lesion in Rats[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(1): 226-234.

References 33

[1]	GIUNTI M,GROSSI G,TROÍA R,et al.Evaluation of serum apolipoprotein A1 in canine sepsis[J].Front Vet Sci,2020,7:263.
[2]	SHA J C,ZHANG H Y,ZHAO Y,et al.Dexmedetomidine attenuates lipopolysaccharide-induced liver oxidative stress and cell apoptosis in rats by increasing GSK-3β/MKP-1/Nrf2 pathway activity via the α2 adrenergic receptor[J].Toxicol Appl Pharmacol,2019,364:144-152.
[3]	FENG X J,GUAN W,ZHAO Y,et al.Dexmedetomidine ameliorates lipopolysaccharide-induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK-3β/Nrf2 signaling pathway[J].J Cell Physiol,2019,234(10):18994-19009.
[4]	张录.右美托咪定对脓毒症大鼠炎症反应的作用及机制的研究[D].南昌:南昌大学,2018.ZHANG L.The effect and the responding mechanism of dexmedetomidine on inflammatory response in rats with sepsis[D].Nanchang:Nanchang University,2018.(in Chinese)
[5]	WANG X R,XU X L,GUO Y H,et al.Qiang Xin 1 formula suppresses excessive pro-inflammatory cytokine responses and microglia activation to prevent cognitive impairment and emotional dysfunctions in experimental sepsis[J].Front Pharmacol,2020,11:579.
[6]	ZHANG H Y,WANG P Y,YU H Y,et al.Aluminum trichloride-induced hippocampal inflammatory lesions are associated with IL-1β-activated IL-1 signaling pathway in developing rats[J].Chemosphere,2018,203:170-178.
[7]	WANG J M,JIANG C,ZHANG K,et al.Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway[J].Free Radic Biol Med,2019,131:345-355.
[8]	CARRASCAL L,NUNEZ-ABADES P,AYALA A,et al.Role of melatonin in the inflammatory process and its therapeutic potential[J].Curr Pharm Des,2018,24(14):1563-1588.
[9]	ASGHARI M H,ABDOLLAHI M,DE OLIVEIRA M R,et al.A review of the protective role of melatonin during phosphine-induced cardiotoxicity:focus on mitochondrial dysfunction,oxidative stress and apoptosis[J].J Pharm Pharmacol,2017,69(3):236-243.
[10]	SHUKLA M,CHINCHALONGPORN V,GOVITRAPONG P,et al.The role of melatonin in targeting cell signaling pathways in neurodegeneration[J].Ann N Y Acad Sci,2019,1443(1):75-96.
[11]	刘亭,毕竟,王盼,等.MAPK/ERK信号通路参与褪黑素对阿尔茨海默病大鼠小脑的神经保护作用[J].中国药理学通报,2019,35(3):402-407.LIU T,BI J,WANG P,et al.Neuroprotective effect of melatonin in cerebellums in Alzheimer's disease animal models via MAPK/ERK signaling pathway[J].Chinese Pharmacological Bulletin,2019,35(3):402-407.(in Chinese)
[12]	WANG Y S,LI Y Y,CUI W,et al.Melatonin attenuates pain hypersensitivity and decreases astrocyte-mediated spinal neuroinflammation in a rat model of oxaliplatin-induced pain[J].Inflammation,2017,40(6):2052-2061.
[13]	LUO J H,SONG J,ZHANG H,et al.Melatonin mediated Foxp3-downregulation decreases cytokines production via the TLR2 and TLR4 pathways in H. pylori infected mice[J].Int Immunopharmacol,2018,64:116-122.
[14]	KARABULUT-BULAN O,BAYRAK B B,ARDA-PIRINCCI P,et al.Role of exogenous melatonin on cell proliferation and oxidant/antioxidant system in aluminum-induced renal toxicity[J].Biol Trace Elem Res,2015,168(1):141-149.
[15]	ZENG J,ZHANG X R,WANG J H,et al.Comparison of Donepezil,Memantine,Melatonin,and Liuwei Dihuang Decoction on behavioral and immune endocrine responses of aged senescence-accelerated mouse resistant 1 mice[J].Front Pharmacol,2020,11:350.
[16]	ZHANG H Y,WEI M,LU X Y,et al.Aluminum trichloride caused hippocampal neural cells death and subsequent depression-like behavior in rats via the activation of IL-1β/JNK signaling pathway[J].Sci Total Environ,2020,715:136942.
[17]	NING Q Q,LIU Z G,WANG X H,et al.Neurodegenerative changes and neuroapoptosis induced by systemic lipopolysaccharide administration are reversed by dexmedetomidine treatment in mice[J].Neurol Res,2017,39(4):357-366.
[18]	ZHENG Y,HE R Y,WANG P,et al.Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization[J].Biomater Sci,2019,7:2037-2049.
[19]	NELSON L H,LENZ K M.Microglia depletion in early life programs persistent changes in social,mood-related,and locomotor behavior in male and female rats[J].Behav Brain Res,2017,316:279-293.
[20]	PARK T,CHEN H Z,KEVALA K,et al.N-Docosahexaenoylethanolamine ameliorates LPS-induced neuroinflammation via cAMP/PKA-dependent signaling[J].J Neuroinflammation,2016,13(1):284.
[21]	PRAKASH D,GOPINATH K,SUDHANDIRAN G.Fisetin enhances behavioral performances and attenuates reactive gliosis and inflammation during aluminum chloride-induced neurotoxicity[J].Neuromolecular Med,2013,15(1):192-208.
[22]	SANTA-CECÍLIA F,SOCIAS B,OUIDJA M O,et al.Doxycycline suppresses microglial activation by inhibiting the p38 MAPK and NF-κB signaling pathways[J].Neurotox Res,2016,29(4):447-459.
[23]	ZHANG D,HU X M,QIAN L,et al.Microglial MAC1 receptor and PI3K are essential in mediating β-amyloid peptide-induced microglial activation and subsequent neurotoxicity[J].J Neuroinflammation,2011,8(1):3.
[24]	ÁLVAREZ-SÁNCHEZ N,CRUZ-CHAMORRO I,DÍAZ-SÁNCHEZ M,et al.Melatonin reduces inflammatory response in peripheral T helper lymphocytes from relapsing-remitting multiple sclerosis patients[J].J Pineal Res,2017,63(4):e12442.
[25]	XU S C,PI H F,ZHANG L,et al.Melatonin prevents abnormal mitochondrial dynamics resulting from the neurotoxicity of cadmium by blocking calcium-dependent translocation of Drp1 to the mitochondria[J].J Pineal Res,2016,60(3):291-302.
[26]	SUWANJANG W,ABRAMOV A Y,CHARNGKAEW K,et al.Melatonin prevents cytosolic calcium overload,mitochondrial damage and cell death due to toxically high doses of dexamethasone-induced oxidative stress in human neuroblastoma SH-SY5Y cells[J].Neurochem Int,2016,97:34-41.
[27]	MAŃKA S,MAJEWSKA E.Immunoregulatory action of melatonin.The mechanism of action and the effect on inflammatory cells[J].Postepy Hig Med Dosw,2016,70:1059-1067.
[28]	ALLAGUI M S,FERIANI A,SAOUDI M,et al.Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats[J].Food Chem Toxicol,2014,70:84-93.
[29]	PARAMEYONG A,GOVITRAPONG P,CHETSA-WANG B.Melatonin attenuates the mitochondrial translocation of mitochondrial fission proteins and Bax,cytosolic calcium overload and cell death in methamphetamine-induced toxicity in neuroblastoma SH-SY5Y cells[J].Mitochondrion,2015,24:1-8.
[30]	PARK E,CHUN H S.Melatonin attenuates manganese and lipopolysaccharide-induced inflammatory activation of BV2 microglia[J].Neurochem Res,2017,42(2):656-666.
[31]	SONG J,KANG S M,LEE K M,et al.The protective effect of melatonin on neural stem cell against LPS-induced inflammation[J].Biomed Res Int,2015,2015:854359.
[32]	CÓRDOBA-MORENO M O,DA SILVA DE SOUZA E,QUILES C L,et al.Rhythmic expression of the melatonergic biosynthetic pathway and its differential modulation in vitro by LPS and IL10 in bone marrow and spleen[J].Sci Rep,2020,10(1):4799.
[33]	SHAO G X,TIAN Y G,WANG H Y,et al.Protective effects of melatonin on lipopolysaccharide-induced mastitis in mice[J].Int Immunopharmacol,2015,29(2):263-268.

Protective Effects of Melatonin on LPS-induced Hippocampal Inflammatory Lesion in Rats

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 33

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	SUN Wenli, WANG Haoqi, ZE Licuo, GAO Yufan, ZHANG Feifan, ZHANG Jian, DUAN Mengqi, SHANG Peng, QIANG Bayangzong. Polymorphism of Pro-Inflammatory Factors (IL-1β, IL-6, TNF-α) in Tibetan Pigs and Its Association Analysis with Immune Traits [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 1958-1969.
[2]	DONG Shucan, MAO Shuaixiang, WU Cuiying, LI Yaokun, SUN Baoli, GUO Yongqing, DENG Ming, LIU Dewu, LIU Guangbin. The Effect of the Androgen Receptor Inhibitor Enzalutamide on Proliferation and Apoptosis of Goat Ovarian Granulosa Cells [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2022-2031.
[3]	YANG Xiaofeng, QIN Xiaowei, LÜ Lihua. Protective Effect of a Derivative of MNQ Against LPS-Induced Inflammatory Injury in Bovine Ovarian Follicular Granulosa Cells in Vitro [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2032-2041.
[4]	LUO Ting, HAN Zhu, XU Yefen, CAI Lin, SUOLANG Sizhu, XU Jinhua, NIU Jiaqiang. Whole Genome Sequencing and Sequence Analysis on T10 of Mycoplasma bovis Strain from Yaks in Xizang [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2154-2167.
[5]	LI Qiuyun, TIAN Xinyuan, LIAO Wensheng, ZHANG Huanrong, REN Yupeng, YANG Falong, ZHU Jiangjiang, XIANG Hua. Effects of SOCS2 on Proliferation, Cycle and Apoptosis of Turbinate Bone Cells in Goats [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2226-2240.
[6]	ZHANG Shengying, LIU Zhongli, GUO Aijiang, WANG Shuai. The Effect of Seven Protease Inhibitors on Activity of DNA Damage Inducible 1 Protein in Echinococcus multilocularis [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2273-2280.
[7]	XIU Haoyu, LI Yingjun, YUAN Kaimin, WANG Chao, YANG Shuhan, Lü Lihua, WANG Dong. Research Progress of Temperature Variation in Different Parts of Body During Estrus in Cows [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1381-1388.
[8]	XIANG Hui, GUI Linsen, YANG Di, WEI Shihao, GONG Yanbin, SHI Yuangang, MA Yun, DAN Xingang. Research Progress on the Estrus Synchronization-fixed-timed Artificial Insemination Technology in Dairy Cows [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1412-1422.
[9]	GUO Xuelian, LI Yongqin, LI Ruiqian, LI Hao, JIN Shuangyuan, WANG Xueyan, DU Jiawei, XU Lihua. Biological Functions of Bovine Respiratory Syncytial Virus G and F Proteins [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1478-1487.
[10]	WANG Zhongbo, LIU Shuang, HE Lixia, FENG Xue, YANG Mengli, WANG Shuzhe, LIU Yuan, FENG Lan, DING Xiaoling, JI Guoshang, YANG Runjun, ZHANG Lupei, MA Yun. Metabolomics Analysis on Different Muscle Tissues of Guyuan Cattle [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1565-1578.
[11]	ZHANG Shuai, CHEN Kuirong, XU Di, JIANG Shan, WANG Mengying, ZHANG Kun, XU Yupei, LEI Guofeng, ZHANG Zhicheng, GUO Meng, ZHAO Yunxiang, LAN Ganqiu, LIANG Jing. Analysis of Microbial Composition Differences in High and Low Feed Conversion Rates Pig Feces based on 16S rRNA Sequencing [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1605-1614.
[12]	ZHANG Chonghao, MA Chang, LI Zhiqiang, WU Gang, ZHANG Yuanshu. The Role and Relationship of Renin-angiotensin System in Gut-vascular Barrier Injury in Ulcerative Colitis Mice [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1756-1765.
[13]	HU Qiaoyan, ZHAI Xiangqin, LI Yidan, HAN Jiale, LEI Chuzhao, DANG Ruihua. Effects of bta-miR-101 on Proliferation, Apoptosis and Secretion of Bovine Testicular Sertoli Cells [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(3): 1040-1051.
[14]	JING Yang, WANG Yumiao, LI Yang, CHANG Hui, MA Zhiqian, LI Zhiwei, XIAO Shuqi. Construction of MARC-145^ORF6 Cell Line Stably Overexpressing PRRSV M Protein and Its Effect on PRRSV Proliferation [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(3): 1159-1169.
[15]	SU Wennan, LIU Jiaqi, ZHONG Jiacheng, CHEN Jidang, ZHU Wanjun, ZHANG Yishan, ZHANG Jipei. Complete Genome Re-sequence and Comparative Genomic Analysis of Avibacterium paragallinarum from Geese [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(3): 1208-1216.