在慢性热应激环境下外源性褪黑素干预对肉鸡皮质酮合成的影响

doi:10.11843/j.issn.0366-6964.2025.11.046

摘要/Abstract

摘要：

本研究旨在探讨外源性褪黑素(melatonin, Mel)对慢性热应激下肉鸡皮质酮合成分泌的机制，为褪黑素缓解慢性热应激提供理论依据。将90只2周龄的肉鸡随机分为6组：正常对照组(CON)，慢性热应激(HS)组，褪黑素干预组：CONH(2.0 mg·kg^-1)组、HSL(0.5 mg·kg^-1)组、HSM(1.0 mg·kg^-1)组、HSH(2.0 mg·kg^-1)组。试验持续21 d。结果表明, 慢性热应激导致肉鸡生产性能下降和血清中皮质酮含量明显升高，而0.5 mg·kg^-1 Mel处理的肉鸡生产性能显著改善(P＜0.001)，HSH组的肉鸡料重比显著下降(P＜0.05)。日粮中补充0.5~2.0 mg·kg^-1 Mel显著降低了慢性热应激下肉鸡血清中皮质酮含量(P＜0.000 1)。此外，Mel能有效改善慢性热应激造成的还原型谷胱甘肽(GSH)含量下降，超氧化物歧化酶(SOD)活性和谷胱甘肽过氧化物酶(GSH-Px)活性下降。根据网络药理学分析，Mel干预慢性热应激，富集到cAMP信号通路，检测到Mel的作用机制与褪黑素受体MT1有关，并通过抑制cAMP/PKA/CREB信号通路，减弱肾上腺皮质酮的合成分泌，减轻应激反应。

关键词: 肉鸡, 慢性热应激, 皮质酮, 外源性褪黑素, 肾上腺

Abstract:

Chronic heat stress seriously affects the production performance of poultry. The purpose of this study was to investigate the mechanism of exogenous melatonin (Mel) on the synthesis and secretion of corticosterone in broilers under chronic heat stress, and to provide a theoretical basis for melatonin to alleviate chronic heat stress. Ninety 2-week-old broilers were randomly divided into 6 groups: normal control group (CON), chronic heat stress (HS) group, melatonin intervention group: CONH (2.0 mg·kg^-1) group, HSL (0.5 mg·kg^-1) group, HSM (1.0 mg·kg^-1) group, HSH (2.0 mg·kg^-1) group. The experiment lasted for 21 days. Results: Chronic heat stress resulted in a decrease in broiler performance and a significant increase in serum corticosterone content, while the performance of broilers treated with 0.5 mg·kg^-1 Mel was significantly improved (P < 0.001), and the feed-to-weight ratio of broilers in the HSH group was significantly decreased (P < 0.05). Dietary supplementation with 0.5-2.0 mg·kg^-1 Mel significantly reduced serum corticosterone content in broilers under chronic heat stress (P < 0.000 1). In addition, Mel could effectively improve the decrease of reduced glutathione (GSH) content, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity caused by chronic heat stress. The network pharmacology analysis showed that Mel intervention in chronic heat stress was enriched in the cAMP signaling pathway. It was detected that the mechanism of Mel was related to the melatonin receptor MT1, and by inhibiting the cAMP/PKA/CREB signaling pathway, the synthesis and secretion of adrenocortical ketone were weakened, and the stress response was alleviated.

Key words: broiler chicken, chronic heat stress, corticosterone, exogenous melatonin, adrenal gland

中图分类号:

S852.2

康欣, 徐向杨, 韩爱格, 宋飞, 芮慧媛, 姜晓文, 葛铭, 于文会. 在慢性热应激环境下外源性褪黑素干预对肉鸡皮质酮合成的影响[J]. 畜牧兽医学报, 2025, 56(11): 5912-5924.

KANG Xin, XU Xiangyang, HAN Aige, SONG Fei, RUI Huiyuan, JIANG Xiaowen, GE Ming, YU Wenhui. Effect of Exogenous Melatonin Intervention on Corticosterone Synthesis in Broilers under Chronic Heat Stress Conditions[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(11): 5912-5924.

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参考文献 45

1	NICLOU M A , CHEN Y K , REDMAN M L . The juxtaposition between heat stress from global warming and human health[J]. J Appl Physiol, 2024, 136 (6): 1346- 1347. doi: 10.1152/japplphysiol.00281.2024
2	TAN X D , LIU R R , ZHAO D , et al. Large-scale genomic and transcriptomic analyses elucidate the genetic basis of high meat yield in chickens[J]. J Adv Res, 2023, 55, 1- 16.
3	VANDANA D G , SEJIAN V , LEES M A , et al. Heat stress and poultry production: impact and amelioration[J]. Int J Biometeorol, 2020, 65 (2): 1- 17.
4	MCKECHNIE A E , WOLF B O . Climate change increases the likelihood of catastrophic avian mortality events during extreme heat waves[J]. Biol Lett, 2010, 6 (2): 253- 256. doi: 10.1098/rsbl.2009.0702
5	CAO X H , GUO L Y , ZHOU C M , et al. Effects of N-acetyl-l-cysteine on chronic heat stress-induced oxidative stress and inflammation in the ovaries of growing pullets[J]. Poult Sci, 2023, 102 (1): 102274. doi: 10.1016/j.psj.2022.102274
6	ZHANG J F , BAI K W , SU W P , et al. Curcumin attenuates heat-stress-induced oxidant damage by simultaneous activation of GSH-related antioxidant enzymes and Nrf2-mediated phase Ⅱ detoxifying enzyme systems in broiler chickens[J]. Poult Sci, 2018, 97 (4): 1209- 1219. doi: 10.3382/ps/pex408
7	ZABOLI G , HUANG X , FENG X , AHN D U . How can heat stress affect chicken meat quality?-a review[J]. Poult Sci, 2019, 98 (3): 1551- 1556. doi: 10.3382/ps/pey399
8	PARDIS N , IDRUS Z , AMAT N J , et al. Environmental temperature and stocking density effects on acute phase proteins, heat shock protein 70, circulating corticosterone and performance in broiler chickens[J]. Int J Biometeorol, 2015, 59 (11): 1577- 1583. doi: 10.1007/s00484-015-0964-3
9	ZAYTSOFF S J M , BORAS V F , UWIERA R R E , et al. A stress-induced model of acute necrotic enteritis in broiler chickens using dietary corticosterone administration[J]. Poult Sci, 2022, 101 (4): 101726. doi: 10.1016/j.psj.2022.101726
10	YUN H , QINWEI S , JIE L , et al. In ovo injection of betaine alleviates corticosterone-induced fatty liver in chickens through epigenetic modifications[J]. Sci Rep, 2017, 7 (1-4): 40251.
11	JOSEPH T T , SCHUCH V , HOSSACK J D , et al. Melatonin: the placental antioxidant and anti-inflammatory[J]. Front Immunol, 2024, 15, 1339304. doi: 10.3389/fimmu.2024.1339304
12	JANA T , DESISLAVA K , PETJ I , et al. The role of melatonin deficiency induced by pinealectomy on motor activity and anxiety responses in young adult, middle-aged and old rats[J]. Behav Brain Funct, 2024, 20 (1): 3. doi: 10.1186/s12993-024-00229-y
13	HARA T , OTSUKA F , TSUKAMOTO-YAMAUCHI N , et al. Mutual effects of melatonin and activin on induction of aldosterone production by human adrenocortical cells[J]. J Steroid Biochem Mol Biol, 2015, 152, 8- 15. doi: 10.1016/j.jsbmb.2015.04.012
14	CLARK W D , CLASSEN H L . The effects of continuously or diurnally fed melatonin on broiler performance and health[J]. Poult Sci, 1995, 74 (11): 1900- 1904. doi: 10.3382/ps.0741900
15	HAO E Y , LIU X L , CHANG L Y , et al. Melatonin alleviates endoplasmic reticulum stress to improve ovarian function by regulating the mTOR pathway in aged laying hens[J]. Poult Sci, 2024, 103 (6): 103703. doi: 10.1016/j.psj.2024.103703
16	ZHOU G , ZHANG J , LIU S , et al. Potential of exogenous melatonin administration to mitigate heat stress induce pathophysiology of chicken[J]. J Therm Biol, 2024, 122, 103883. doi: 10.1016/j.jtherbio.2024.103883
17	BAI M , LIU H , XU K , et al. A review of the immunomodulatory role of dietary tryptophan in livestock and poultry[J]. Amino Acids, 2017, 49 (1): 67- 74. doi: 10.1007/s00726-016-2351-8
18	WU Q , YANG F , TANG H . Based on network pharmacology method to discovered the targets and therapeutic mechanism of Paederia scandens against nonalcoholic fatty liver disease in chicken[J]. Poult Sci, 2021, 100 (4): 101042. doi: 10.1016/j.psj.2021.101042
19	ZHANG H Y , KONG Q B , WANG J , et al. Complex roles of cAMP-PKA-CREB signaling in cancer[J]. Exp Hematol Oncol, 2020, 9 (1): 32. doi: 10.1186/s40164-020-00191-1
20	OKAMOTO H H , CECON E , NUREKI O , et al. Melatonin receptor structure and signaling[J]. J Pineal Res, 2024, 76 (3): e12952. doi: 10.1111/jpi.12952
21	JIN W , MA R , ZHAI L , et al. Ginsenoside Rd attenuates ACTH-induced corticosterone secretion by blocking the MC2R-cAMP/PKA/CREB pathway in Y1 mouse adrenocortical cells[J]. Life Sci, 2020, 245 (C): 117337.
22	MANGAN M , SIWEK M . Strategies to combat heat stress in poultry production-A review[J]. J Anim Physiol Anim Nutr (Berl), 2023, 108 (3): 576- 595.
23	NAWAB A , IBTISHAM F , LI G , et al. Heat stress in poultry production: Mitigation strategies to overcome the future challenges facing the global poultry industry[J]. J Therm Biol, 2018, 78, 131- 139. doi: 10.1016/j.jtherbio.2018.08.010
24	MAJID S , HUU H L . Deleterious effects of heat stress on poultry production: unveiling the benefits of betaine and polyphenols[J]. Poultry, 2022, 1 (3): 147- 156. doi: 10.3390/poultry1030013
25	ROUSHDY M E , ZAGLOOL W A , EL-TARABANY S M . Effects of chronic thermal stress on growth performance, carcass traits, antioxidant indices and the expression of HSP70, growth hormone and superoxide dismutase genes in two broiler strains[J]. J Therm Biol, 2018, 74, 337- 343. doi: 10.1016/j.jtherbio.2018.04.009
26	SHAN X , XU X , WANG L , et al. Dietary curcumin supplementation attenuates hepatic damage and function abnormality in a chronic corticosterone-induced stress model in broilers[J]. J Steroid Biochem Mol Biol, 2024, 243, 106579. doi: 10.1016/j.jsbmb.2024.106579
27	ZHANG R , SUN J , WANG Y , et al. Ameliorative effect of phenolic compound-pterostilbene on corticosterone-induced hepatic lipid metabolic disorder in broilers[J]. J Nutr Biochem, 2024, 137, 109822.
28	BALLUR A F H , ALTINOZ E , YIGITTURK G , et al. Influence of pinealectomy and long-term melatonin administration on inflammation and oxidative stress in experimental gouty arthritis[J]. Inflammation, 2022, 45 (3): 1332- 1347. doi: 10.1007/s10753-022-01623-2
29	ZIAEI S , HASANI M , MALEKAHMADI M , et al. Effect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials[J]. J Ovarian Res, 2024, 17 (1): 138. doi: 10.1186/s13048-024-01450-z
30	ANDERSEN L P , GÖGENUR I , ROSENBERG J , et al. The safety of melatonin in humans[J]. Clin Drug Investig, 2016, 36 (3): 169- 175. doi: 10.1007/s40261-015-0368-5
31	FISCHER T W , KLESZCZYN'SKI K , HARDKOP L H , et al. Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin[J]. J Pineal Res, 2013, 54 (3): 303- 312. doi: 10.1111/jpi.12018
32	BOCHEVA G , BAKALOV D , ILIEV P , et al. The vital role of melatonin and its metabolites in the neuroprotection and retardation of brain aging[J]. Int J Mol Sci, 2024, 25 (10): 5122. doi: 10.3390/ijms25105122
33	CHIN K V , YANG W L , RAVATN R , et al. Reinventing the wheel of cyclic AMP: novel mechanisms of cAMP signaling[J]. Ann N Y Acad Sci, 2002, 968 (1): 49- 64. doi: 10.1111/j.1749-6632.2002.tb04326.x
34	TSE H L , CHEUNG T S , LEE S , et al. Real-time determination of intracellular cAMP reveals functional coupling of G_s protein to the melatonin MT₁ receptor[J]. I Int J Mol Sci, 2024, 25 (5): 2919. doi: 10.3390/ijms25052919
35	LEWIS A E , AESOY R , BAKKE M . Role of EPAC in cAMP-mediated actions in adrenocortical cells[J]. Front Endocrinol, 2016, 7, 63.
36	CHEN D , WANG J , CAO J , et al. cAMP-PKA signaling pathway and anxiety: Where do we go next?[J]. Cell Sign, 2024, 122, 111311. doi: 10.1016/j.cellsig.2024.111311
37	KHANNPNAVAR B , MEHTA V , QI C , et al. Structure and function of adenylyl cyclases, key enzymes in cellular signaling[J]. Curr Opin Str Biol, 2020, 63, 34- 41. doi: 10.1016/j.sbi.2020.03.003
38	STWORA K K , KOZLOWSKA A , JASTRZABEK D , et al. Impact of endocrine-active compounds on adrenal androgen production in pigs during neonatal period[J]. Environ Toxicol Pharmacol, 2024, 107, 104435- 104435. doi: 10.1016/j.etap.2024.104435
39	PIHLAJOKI M , DÖRNER J , COCHRAN R S , et al. Adrenocortical zonation, renewal, and remodeling[J]. Front Endocrinol, 2015, 6, 27.
40	LIM H S , LEE S H , SEO H , et al. Early stage ultraviolet irradiation damage to skin collagen can be suppressed by HPA axis control via controlled CYP11B[J]. Biomed Pharmacother, 2022, 155, 113716. doi: 10.1016/j.biopha.2022.113716
41	IRENE M , ALFONSO B G , JULIA C , et al. Pharmacokinetics of exogenous melatonin in relation to formulation, and effects on sleep: a systematic review[J]. Sleep Med Rev, 2021, 57, 101431- 101431. doi: 10.1016/j.smrv.2021.101431
42	ANDERSEN L P , WERNER M U , ROSENKILDE M M , et al. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers[J]. BMC Pharmacol Toxicol, 2016, 17 (1): 8. doi: 10.1186/s40360-016-0052-2
43	SÉBASTIEN L , CLAIRE F , M G A , et al. Melatonin: From pharmacokinetics to clinical use in autism spectrum disorder[J]. Int J Mol Sci, 2021, 22 (3): 1490. doi: 10.3390/ijms22031490
44	荆瀛黎, 武清斌, 苑晓晨, 等. 褪黑素对人体睡眠和血压的影响[J]. 现代生物医学进展, 2013, 13 (11): 2165- 2167.
	JING Y L , WU Q B , YUAN X C , et al. The effect of melalonin on human sleep and blood pressure[J]. Progress in Modern Biomedicine, 2013, 13 (11): 2165- 2167.
45	ZISAPEL N . New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation[J]. Br J Pharmacol, 2018, 175 (16): 3190- 3199. doi: 10.1111/bph.14116

抗体 Antibodys	来源 Source	货号 Identifier	稀释比例 Dilution ratio
Anti-HSP70 antibody	Bioss	bs-0244R	1∶1 000
Anti-MT1 antibody	Bioss	bs-0027R	1∶1 000
Anti-MT2 antibody	Bioss	bs-0963R	1∶1 000
Anti-PKA antibody	Bioss	bs-0520R	1∶1 000
Anti-CYP11A1 antibody	Bioss	bs-3608R	1∶1 000
Anti-CREB antibody	Wanleibio	WL01848	1∶1 000
Anti-CYP11B1 antibody	Wanleibio	WL05422	1∶1 000
Anti-P-CREB antibody	Abways	CY5043	1∶1 000
Anti-StAR antibody	Abclonal	A22166	1∶2 000
Anti-Rabbit IgG H&L antibody	Bioss	bs-0295G-HRP	1∶10 000
Anti-Beta tubulin antibody	Bioss	bs-4511R	1∶10 000

基因名称 Gene names	序列(5′ → 3′) Sequence	方向 Orientation	NCBI编号 NCBI No.
GAPDH	TATCTTCCAGGAGCGTGAC	Forward	NM_204305.2
	ATCTGCCCATTTGATGTTGC	Reverse
MT1	TCCTGGTCATCCTCTCGGT	Forward	NM_205362.2
	CGTTCCGCAGTTTCTTGTTG	Reverse
MT2	TGCTGATCTTCACCACCGT	Forward	NM_001293103.2
	AGGTTGCCCAAAATGTCCAC	Reverse
PKA	ATCACGTCTCTGAACTTGCT	Forward	XM_025152948.2
	ACTCTTCCGAATGATCCTGT	Reverse
CREB	CTAATAAGGCAGTAGATACCG	Forward	XM_040653773.2
	GAACACGTTTAACTTCCACT	Reverse
CYP11A1	TGGCTCAACCTGTACCACT	Forward	NM_001001756.2
	ACGTTGTGGAAGCCTCCCTC	Reverse
HSD3B1	CCCTCAATCATCCCCAGA	Forward Reverse	XM_046906757.1
	TTATTCAACATCTCCGTGCT	Reverse

项目Item	组别Group
项目Item	CON	CONH	HS	HSL	HSM	HSH
0-7 d ADG	57.14±4.59	48.57±4.19	42.38±2.42	44.76±1.67	49.05±2.68	32.62±6.67
7-14 d ADG	51.11±5.96	61.98±2.63	51.98±3.02	55.02±4.68	38.10±1.46	39.60±1.93
14-21 d ADG	78.17±3.61	57.22±2.24^*	38.49±3.95^####	63.17±3.79^@@	53.25±4.40	46.35±2.01
0-21 d ADG	62.14±1.17	55.93±1.20	44.29±1.55^###	54.32±2.91^@	46.80±0.88	39.52±1.85
胸肌指数/% Breast muscle index	0.182±0.001	0.165±0.005	0.161±0.006	0.143±0.002	0.165±0.008	0.192±0.006^@
F/G	2.770±0.028	2.624±0.058	2.783±0.028	2.671±0.028	2.802±0.010	2.587±0.065^@

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