目的 探讨山茛菪碱在缺氧缺血性脑损伤幼龄鼠脑组织形态和功能损伤中的调控作用。 方法 50只幼龄大鼠均分为健康对照组、模型组、模型加药组（尾静脉注射山莨菪碱2.5、5、10 mg/kg）共5组。脑组织干湿重法检测脑指数和脑含水率，HE染色观察脑组织病理损伤，TUNEL染色观察脑海马神经元周围组织细胞凋亡情况，Western blot检测脑组织中Bax/Bcl-2、caspase-9、caspase-3、BDNF和NGF蛋白表达水平，RT-PCR检测BDNF和NGF mRNA表达水平，试剂盒检测SOD、MDA和GSH-Px含量。 结果 与健康对照组比较，模型组幼龄鼠脑组织形态和神经功能损伤严重（P<0.05）。与模型组比较，5 mg/kg和10 mg/kg山茛菪碱组脑指数和脑含水率降低（P<0.05），脑组织病理损伤好转，脑海马神经元周围组织细胞凋亡减少，Bax/Bcl-2、caspase-9、caspase-3表达水平降低（P<0.05），BDNF和NGF表达水平增高（P<0.05），MDA含量降低，SOD和GSH-Px含量增高（P<0.05）。 结论 山茛菪碱能够缓解缺氧缺血性脑损伤幼龄鼠脑组织形态和功能损伤。
Abstract
Objective To investigate the regulatory effect of anisodamine on brain injury and neurological damage in young rats with hypoxic-ischemic brain damage. Methods Fifty young rats were divided into five groups (n=10): a healthy control group, a model group, and three model dosing groups (intravenously injected anisodamine for 2.5, 5, 10 mg/kg). Brain tissue wet and dry weight method was used to detect brain index and brain water content. HE staining was used to observe the pathological damage of brain tissue. TUNEL staining was used to observe the apoptosis of brain tissues around hippocampal neurons. Western blot detects the protein expression levels of Bax/Bcl-2, caspase-9, caspase-3, BDNF and NGF in brain tissue. RT-PCR was used to detect the expression level of BDNF and NGF mRNA, and the kit was used to detect the content of SOD, MDA and GSH-Px. Results Compared with the healthy control group, the brain tissue and nerve function of young rats in the model group were seriously damaged (P<0.05). Compared with the model group, the brain index and brain water content of young rats in the 5 mg/kg and 10 mg/kg anisodamine groups significantly reduced (P<0.05). The pathological damage of the brain tissue significantly improved, and the apoptotic cells around the hippocampal neurons in the brain Apoptosis decreased, Bax/Bcl-2, caspase-9, and caspase-3 expression levels decreased (P<0.05), BDNF and NGF expression levels increased (P<0.05), MDA content decreased, SOD and GSH-Px content increased (P<0.05). Conclusions Anisodamine can alleviate brain damage and nerve function damage in young rats with HIBD.
关键词
山茛菪碱 /
缺氧缺血性脑损伤 /
幼龄鼠模型
Key words
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Anisodamine /
Hypoxic-ischemic brain damage /
Young rats model
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参考文献
[1] 薛磊, 沈冰冰, 王丽娜, 等. 黄芩苷对新生大鼠缺氧缺血性脑损伤保护作用的实验研究[J]. 解放军医药杂志, 2019, 31(10): 6-9. DOI: 10.3969/j.issn.2095-140X.2019.10.002.
[2] Hamdy N, Eide S, Sun HS, et al. Animal models for neonatal brain injury induced by hypoxic ischemic conditions in rodents[J]. Exp Neurol, 2020, 334: 113457. DOI: 10.1016/j.expneurol.2020.113457.
[3] Bustelo M, Barkhuizen M, van den Hove DLA, et al. Clinical implications of epigenetic dysregulation in perinatal hypoxic-ischemic brain damage[J]. Front Neurol, 2020, 11: 483. DOI: 10.3389/fneur. 2020. 00483.
[4] Go H, Saito Y, Maeda H, et al. Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy[J]. J Neonatal Perinatal Med, 2021, 14(2): 177-182. DOI: 10.3233/NPM-200431.
[5] Cho KH, Davidson JO, Dean JM, et al. Cooling and immunomodulation for treating hypoxic-ischemic brain injury[J]. Pediatr Int, 2020, 62(7): 770-778. DOI: 10.1111/ped.14215.
[6] Li Z, Xu CY, Tao YZ, et al. Anisodamine alleviates lipopolysaccharide-induced pancreatic acinar cell injury through NLRP3 inflammasome and NF-κB signaling pathway[J]. J Recept Signal Transduct Res, 2020, 40(1): 58-66. DOI: 10.1080/10799893.2020.1713808.
[7] Li YF, Xu BY, An R, et al. Protective effect of anisodamine in rats with glycerol-induced acute kidney injury[J]. BMC Nephrol, 2019, 20(1): 223. DOI: 10.1186/s12882-019-1394-y.
[8] Xu ZW, Wang T, Chen L, et al. Treatment of dilated cardiomyopathy caused by coronary microvascular dysfunction with anisodamine: a report of 5 cases[J]. J Tradit Chin Med, 2020, 40(2): 340-342. PMID: 32242401.
[9] Liu C, Shen FM, Le YY, et al. Antishock effect of anisodamine involves a novel pathway for activating alpha7 nicotinic acetylcholine receptor[J]. Crit Care Med, 2009, 37(2): 634-641. DOI: 10.1097/CCM.0b013e31819598f5.
[10]Li XL, Hong M. Aqueous extract of Dendrobium officinale confers neuroprotection against hypoxic-ischemic brain damage in neonatal rats[J]. Kaohsiung J Med Sci, 2020, 36(1): 43-53. DOI: 10.1002/kjm2.12139.
[11]Zhao Q, Cheng X, Wang X, et al. Neuroprotective effect and mechanism of Mu-Xiang-You-Fang on cerebral ischemia-reperfusion injury in rats[J]. J Ethnopharmacol, 2016, 192: 140-147. DOI: 10.1016/j.jep.2016.07.016.
[12]Fang H, Li HF, Yang M, et al. microRNA-128 enhances neuroprotective effects of dexmedetomidine on neonatal mice with hypoxic-ischemic brain damage by targeting WNT1[J]. Biomed Pharmacother, 2019, 113: 108671. DOI: 10.1016/j.biopha.2019.108671.
[13]Hou X, Yuan Z, Wang X, et al. Peptidome analysis of cerebrospinal fluid in neonates with hypoxic-ischemic brain damage[J]. Mol Brain, 2020, 13(1): 133. DOI: 10.1186/s13041-020-00671-9.
[14] 杜逸亭, 高淑强, 李彪, 等. 高压氧联合GM-1治疗对新生儿缺血缺氧性脑病患儿血清Bcl-2、NSE和NF-κB的影响[J]. 解放军医药杂志, 2017, 29(12): 61-63. DOI: 10.3969/j.issn.2095-140X.2017.12.017.
[15] 闫继宏, 王勇. 促红细胞生成素治疗新生儿缺氧缺血性脑病的研究进展[J]. 临床误诊误治, 2017, 30(11): 112-116. DOI: 10.3969/j.issn.1002-3429.2017.11.033.
[16]Dumbuya JS, Chen L, Shu SY, et al. G-CSF attenuates neuroinflammation and neuronal apoptosis via the mTOR/p70SK6 signaling pathway in neonatal Hypoxia-Ischemia rat model[J]. Brain Res, 2020, 1739: 146817. DOI: 10.1016/j. brainres.2020.146817.
[17]邱玲, 范方毅, 邓锐, 等. miR-181a-5p对T淋巴细胞白血病Jurkat细胞增殖和凋亡的影响[J]. 临床误诊误治, 2019, 32(3): 40-45. DOI: 10.3969/j.issn.1002-3429.2019.03.010.
[18]Zhang C, Ni S, Yang ZC, et al. Oxidative stress induces chondrocyte apoptosis through caspase-dependent and caspase-independent mitochondrial pathways and the antioxidant mechanism of angelica sinensis polysaccharide[J]. Oxid Med Cell Longev, 2020: 3240820. DOI: 10.1155/2020/3240820.
[19]Jaldeep L, Lipi B, Prakash P. Potential role of NGF, BDNF and their receptors in oligodendrocytes differentiation from neural stem cell an in vitro study[J]. Cell Biol Int, 2021, 45(2): 432-446. DOI: 10.1002/cbin.11500.
[20]Wang XX, Cong PX, Wang XC, et al. Maternal diet with sea urchin gangliosides promotes neurodevelopment of young offspring via enhancing NGF and BDNF expression[J]. Food Funct, 2020, 11(11): 9912-9923. DOI: 10.1039/d0fo01605e.
[21]Kong ZL, Hsu YT, Johnson A, et al. Protective effects of Antrodia camphorata extract against hypoxic cell injury and ischemic stroke brain damage[J]. Phytother Res, 2021, 35(3): 1609-1620. DOI: 10.1002/ptr.6928.
[22]Hu X, Li SR, Doycheva DM, et al. Rh-CSF1 Attenuates oxidative stress and neuronal apoptosis via the CSF1R/PLCG2/PKA/UCP2 signaling pathway in a rat model of neonatal HIE[J]. Oxid Med Cell Longev, 2020, 2020: 6801587. DOI: 10.1155/2020/6801587.
[23]Le K, Song ZP, Deng J, et al. Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation[J]. Inflamm Res, 2020, 69(12): 1201-1213. DOI: 10.1007/s00011-020-01402-5.
基金
重庆市技术创新与应用发展专项重点项目（cstc2019 jscx-gksbX0064）
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