首页|天麻素对大鼠分娩镇痛及新生鼠缺血、缺氧性脑损伤的影响及相关机制

天麻素对大鼠分娩镇痛及新生鼠缺血、缺氧性脑损伤的影响及相关机制

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目的 探讨天麻素(gastrodin,GAS)对大鼠分娩镇痛及新生鼠缺血、缺氧性脑损伤的影响及可能的作用机制。方法 将60只妊娠大鼠随机分为空白组、GAS低剂量组、GAS中剂量组、GAS高剂量组和阳性对照组,各12只。产程开始后GAS低剂量组、GAS中剂量组和GAS高剂量组分别腹腔注射50、100、150 mg·kg-1 GAS注射液(用生理盐水配制),阳性对照组尾静脉注射盐酸瑞芬太尼5 μg·kg-1,空白组给予等量生理盐水。用热水甩尾法测定大鼠分娩痛阈值;用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测各组大鼠肿瘤坏死因子-α(tumour necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-6(interleukin-6,IL-6)的水平;用实时荧光定量PCR(quantitative real-time polymerase chain reaction,RT-qPCR)和蛋白印迹法(Western blotting)检测大鼠脊髓组织中核因子-κB p65(NF-κB p65)、磷酸化核因子-κB p65(p-NF-κB p65)、NOD样受体蛋白3(NOD like receptor protein 3,NLRP3)mRNA和蛋白表达的情况;用Morris水迷宫实验评定各组新生鼠的学习记忆能力;测定各组新生鼠脑组织的含水量;用HE染色观察各组新生鼠海马组织CA1区的病理变化。结果 与空白组比较,GAS高、中、低剂量组和阳性对照组大鼠痛阈值、新生鼠跨台次数升高,TNF-α、IL-1β、IL-6、p-NF-κB p65蛋白表达、NF-κB p65 mRNA表达、NLRP3 mRNA和蛋白表达水平、新生鼠逃避潜伏期和脑组织含水量均明显降低(P<0。05)。与GAS低剂量组比较,GAS中剂量组、GAS高剂量组和阳性对照组的TNF-α、IL-1β、IL-6、p-NF-κB p65蛋白表达、NF-κB p65 mRNA表达、NLRP3 mRNA和蛋白表达水平、新生鼠逃避潜伏期和脑组织含水量均明显降低(P<0。05)。与GAS中剂量组比较,GAS高剂量组和阳性对照组TNF-α、IL-1β、IL-6、p-NF-κB p65蛋白表达、NF-κB p65 mRNA表达、NLRP3 mRNA和蛋白表达水平、新生鼠逃避潜伏期和脑组织含水量也明显降低(P<0。05),而GAS高剂量组与阳性对照组比较差异无统计学意义(P>0。05)。结论 GAS能够降低分娩大鼠产程中对疼痛的敏感度,减少促炎因子表达,改善神经炎症,缓解新生鼠脑损伤,可能是通过抑制NF-κB/NLRP3信号通路发挥作用的。
Effects and mechanism of gastrodin on labor analgesia in rats and on hypoxic-ischemic brain injury in neonatal rats
Objective To investigate the effects of gastrodin(GAS)on labor analgesia in rats and on hypoxic-ischemic brain injury in neonatal rats and its possible mechanism.Methods Sixty pregnant rats were randomly divided into blank group,low,medium and high dose of GAS groups and positive control group,with 12 rats in each group.After the beginning of labor,50,100 and 150 mg·kg-1 GAS(prepared with normal saline)was injected intraperitoneally in the low,medium and high dose of GAS group,remifentanil hydrochloride 5 μg·kg-1 was injected into the tail vein of the positive control group,and same amount of normal saline was given to the blank group.The pain threshold of delivery was measured by hot water tail flicking method.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)was detected by enzyme linked immunosorbent assay(ELISA).The mRNA and protein expressions of nuclear factors-κB p65(NF-κB p65),phosphorylated nuclear factors-κB p65(p-NF-κB p65)and NOD like receptor protein 3(NLRP3)in rat hippocampus were detected by quantitative real-time polymerase chain reaction(RT-qPCR)and Western blotting.The learning and memory ability of neonatal rats was evaluated by Morris water maze test.The pathological changes of hippocampal CA1 area of rats were observed by HE staining.The brain water content of neonatal rats was measured.Results Compared with the blank group,the pain threshold and neonatal rat number of crossing platform were increased,the levels of TNF-α,IL-1β,IL-6,and p-NF-κB p65 protein expression,NF-κB p65 mRNA expression,NLRP3 mRNA and protein,neonatal rat escape latency and brain water content were decreased in low,medium and high dose of GAS group and positive control group(P<0.05).Compared with the low dose of GAS group,the TNF-α,IL-1β,IL-6,and p-NF-κB p65 protein expression,NF-κB p65 mRNA expression,NLRP3 mRNA and protein,neonatal rat escape latency and brain water content were decreased in medium and high dose of GAS group and positive control group(P<0.05).Compared with the medium dose of GAS group,the TNF-α,IL-1β,IL-6,and p-NF-κB p65 protein expression,NF-κB p65 mRNA expression,NLRP3 mRNA and protein,neonatal rat escape latency and brain water content were decreased in high dose of GAS group and positive control group(P<0.05).Compared with the positive control group,there was no significant difference in the above indexes(P>0.05).Conclusion GAS can reduce the sensitivity to pain,reduce the expression of proinflammatory factors,improve neuroinflammation and reduce brain injury in neonatal rats,possibly by inhibiting NF-κB/NLRP3 signaling pathway.

labor analgesiaischemic hypoxic brain injurygastrodinnuclear factor-κBNOD like receptor protein 3

苗艳、李笑媛、张欣

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沧州市人民医院产科,沧州 061001

分娩镇痛 缺血缺氧性脑损伤 天麻素 核因子-κB NOD样受体蛋白3

2021年度河北省医学科学研究课题计划项目

20210430

2024

西北药学杂志
西安交通大学,陕西省药学会

西北药学杂志

CSTPCD
影响因子:0.912
ISSN:1004-2407
年,卷(期):2024.39(4)