| 引用本文:刘尧1，张建军1，李振皓2，朱映黎1，张睿1，乐娜1，陈彦1，陈亚文1，陶然1，王淳1，李明焱2，王林元1.川芎对衰老大鼠脑保护作用及对PI3K/AKT/HIF-1α通路的影响[J].世界中医药,2023,(01):. |
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| 川芎对衰老大鼠脑保护作用及对PI3K/AKT/HIF-1α通路的影响 |
| Protective Effect of Ligusticum chuanxiong on Brain of Aging Rats and Its Impact on PI3K/AKT/HIF-1α Pathway |
| 投稿时间：2022-11-15 |
| DOI：10.3969/j.issn.1673-7202.2023.01.008 |
| 中文关键词: 川芎 久服 剂量 衰老 活血化瘀 抗氧化 |
| English Keywords:Ligusticum chuanxiong Hort Long-term administration Dose Aging Activating blood and resolving stasis Antioxidation |
| 基金项目:国家重点研发计划（2018YFC1706800） |
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| 中文摘要: |
| 目的：通过构建衰老合并血瘀大鼠模型，探讨川芎小剂量久服对于延缓衰老脑保护的药效及作用机制，为川芎的临床用药提供依据。方法：将66只SD大鼠分为空白组、模型组、维生素E组、川芎2 g组、川芎4 g组、川芎配伍人参2 g组，每组11只。除空白组外各组腹腔注射D-半乳糖（300 mg/kg）连续42 d，同时继续造模并给药14 d，第15天冰水浴20 min，连续14 d，最后1 d注射0.1%肾上腺素0.8 mg/kg。WST-1法检测血清超氧化物歧化酶（SOD）、比色法检测谷胱甘肽过氧化物酶（GSH-Px）活性、总抗氧化能力（T-AOC），TBA法检测脂质过氧化产物丙二醛（MDA），酶联免疫吸附试验检测蛋白质羰基（PC）含量，酶联免疫吸附试验检测脑组织一氧化氮（NO）、内皮型一氧化氮合酶(eNOS)、血栓素B2(TXB2)、内皮素（ET）-1含量。蛋白质印迹法（Western Blotting）测定检测脑组织磷脂酰肌醇3激酶（PI3K）蛋白、蛋白激酶B（AKT）蛋白、缺氧诱导因子-1α（HIF-1α）表达量。结果：与空白组比较，模型组体质量下降（P<0.001），血清SOD、GSH-PX、T-AOC含量降低（P<0.001，P<0.01，P<0.01），MDA、PC含量升高（P<0.001），脑组织NO、TXB2、ET-1含量升高（P<0.001，P<0.05，P<0.001），eNOS含量降低（P<0.01），HIF-1α表达量降低（P<0.05）；与模型组比较，川芎2 g及4 g能升高血清GSH-Px含量，增加T-AOC，降低脑组织NO、TXB2、ET-1含量，升高eNOS（P<0.01），川芎4 g可以增加HIF-1α蛋白表达量（P<0.01）。川芎1 g与人参1 g配伍后进一步升高血清SOD、GSH-Px含量，降低血清MDA、PC含量，降低脑组织NO、TXB2、ET-1含量（P<0.001，P<0.05，P<0.001），升高eNOS（P<0.001），增加HIF-1α蛋白表达量（P<0.01）。结论：对衰老合并血瘀大鼠模型，川芎小剂量久服即可改善内皮功能，抑制氧化应激，发挥抗氧化作用；川芎剂量减少并与人参配伍后可以起到协同增效作用，可能通过HIF-1α通路对脑起到保护作用。 |
| English Summary: |
| To observe the protective effect and mechanism of low-dose Ligusticum chuanxiong for long-term administration on delaying aging brain by constructing an aging rat model with blood stasis，to provide a basis for clinical medication of L.chuanxiong.Methods:A total of 66 SD rats were divided into blank group，model group，vitamin E group，2 g L.chuanxiong group，4 g L.chuanxiong group and 2 g L.chuanxiong+Panax ginseng group，with 11 in each group.All groups，except the blank group，were given D-galactose(300 mg/kg，ip) for 42 consecutive days，during which drugs were administered for 14 days.On the 15th day，the rats were given ice water bath for 20 minutes for 14 consecutive days，and 0.1% of 0.8 mg/kg adrenaline was injected on the last day.Serum superoxide dismutase(SOD) was detected by WST-1 assay，and the glutathione peroxidase(GSH-Px) activity and total antioxidant capacity(T-AOC) was detected by colorimetry.Malondialdehyde(MDA)，a product of lipid peroxidation，was detected by thiobarbituric acid(TBA) method.Enzyme-linked immunosorbent assay was performed to determine the content of protein carbonyl compounds(PC) and the contents of nitric oxide(NO)，endothelial nitric oxide synthase(eNOS)，thromboxane B2(TXB2) and endothelin-1(ET-1) in brain tissue.Western blot was used to detect the expressions of phosphatidylinositol 3-kinase(PI3K)，protein kinase B(AKT) and hypoxia-inducible factor 1α(HIF-1α) in brain tissue.Results:Compared with the blank group，the model group had decreased body weight(P<0.001)，lowered SOD，GSH-Px and T-AOC(P<0.001，P<0.01，P<0.01)，eNOS(P<0.01) and HIF-1α(P<0.05) and increased MDA and PC(P<0.001) and NO，TXB2 and ET-1(P<0.001，P<0.05，P<0.001).Compared with the model group，2 g and 4 g L.chuanxiong up-regulated GSH-Px，enhanced T-AOC，reduced NO，TXB2 and ET-1，and elevated eNOS(P<0.01).In addition，4 g L.chuanxiong increased HIF-1α(P<0.01).After combination of 1 g L.chuanxiong and 1 g P.ginseng，SOD and GSH-Px were elevated，while MDA and PC were lowered; there was a decrease in NO，TXB2 and ET-1(P<0.001，P<0.05，P<0.001) while an increase in eNOS(P<0.001); HIF-1α was increased(P<0.01).Conclusion:For the aging rat model with blood stasis，low-dose L.chuanxiong can improve endothelial function and inhibit oxidative stress，exerting an antioxidant effect.L.chuanxiong at a reduced dose plays a synergistic role with P.ginseng，which may protect the brain through HIF-1α pathway. |
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