柴胡桂枝汤挥发油对Fmr1基因敲除小鼠的治疗作用和机制探讨
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摘要
目的研究Fmr1小鼠是否存在与人类脆性X综合征(FXS)患者相似的异常行为,评价是否可以作为FXS的疾病模型。
方法以PCR和免疫印迹技术对Fmr1基因敲除(KO)小鼠和野生型(WT)小鼠进行基因型鉴定；HE和Go1gi染色方法分别观察2组动物睾丸和脑内树突棘形态；分别对实验动物进行听源性惊厥(AGS)观察,以水迷宫、避暗、跳台方法检测动物学习记忆水平,以旷场、高架十字迷宫和自主活动实验检测动物探索行为能力。
结果WT小鼠扩增出预期约为500bp的DNA片断,KO小鼠则是800bp的DNA片断,KO小鼠无FMRP蛋白表达,树突棘长度明显增长,密度显著增加,KO雄性小鼠有巨睾征；AGS易感性比WT明显增高(P<0.05)；Morris水迷宫实验的定向航行实验显示,KO小鼠的潜伏期和穿越平台次数与WT小鼠相比有明显增多(P<0.05)；空间搜索实验显示,KO小鼠在目标象限停留时间明显短于WT小鼠的停留时间(P<0.05)；避暗实验和跳台实验显示,KO小鼠潜伏期明显短于WT小鼠,而错误次数明显增多(P<0.05)；旷场实验显示,KO小鼠在中央区域停留时间及进入次数明显多于WT小鼠(P<0.05)；KO小鼠与WT小鼠相比,总运动路程明显增多,速度明显增快(P<0.05)；高架十字迷宫实验显示,KO小鼠在开放臂活动时间、次数以及路程均明显多于WT小鼠(P<0.05)；自主活动实验显示,KO小鼠的活动次数明显多于WT小鼠(P<0.05),而站立次数明显少于WT小鼠(P<0.05)。
结论从基因型、蛋白表达谱、形态学及行为学等方面结果提示Fmrl基因敲除小鼠具有人类脆性X综合征类似的表型,可作为FXS疾病模型用于论文的后续研究,而且这些表型与FMRP表达缺失有关。
目的观察柴胡桂枝汤挥发油对Fmr1基因敲除小鼠异常行为的干预。
方法利用超临界CO2萃取技术制备柴胡桂枝汤挥发油并用GC-MS分析鉴定柴胡桂枝汤挥发油成分；4周龄KO及WT小鼠按处理方式的不同被随机分为药物处理组(即腹腔注射柴胡桂枝汤挥发油)、溶媒对照组(即腹腔注射植物油)及空白对照组(即不给予任何处理)。药物处理组进一步按所给浓度的不同继续分组,分别对各组动物在给药后进行避暗、跳台、高架十字迷宫、旷场、自主活动和AGS等行为学观察。
结果经GC-MS分析鉴定柴胡桂枝汤挥发油含有28种组分。其中,最主要成分姜辣素占31.94%,丁香酚占18.01%,单萜类物质占12.34%,3-丁基-1(3H)-异苯并呋喃酮占9.34%,肉桂类物质占8.03%。
旷场实验显示,随柴胡桂枝汤挥发油浓度的增加,KO和WT小鼠的平均速度、穿越中央格次数、总路程等逐渐降低。高架十字迷宫实验显示,KO小鼠给予柴胡桂枝汤挥发油处理后,与KO溶媒组相比,KO小鼠在开放区域活动时间、次数以及路程均降低,有显著的统计学差异(P<0.05)。自主活动实验显示,使用柴胡桂枝汤挥发油后,KO小鼠的活动次数明显减少,动物站立次数明显增多(P<0.05)；跳台实验显示,柴胡桂枝汤挥发油处理后,KO小鼠潜伏期和错误次数有明显改善(P<0.05),WT小鼠潜伏期和错误次数有较少改善。避暗实验中,柴胡桂枝汤挥发油处理后,KO小鼠潜伏期延长(P<0.05),错误次数减少(P<0.05),WT小鼠潜伏期和错误次数无明显改善(P>0.05)。听源性惊厥实验中,随柴胡桂枝汤挥发油浓度的增加,KO小鼠的AGS的潜伏期延长,发作程度降低(P<0.05),1.5mg/g浓度的柴胡桂枝汤挥发油能完全抑制AGS的发生。
结论柴胡桂枝汤挥发油可以改善KO小鼠AGS和运动过多的发生,改善学习记忆能力,对KO小鼠的异常行为有一定治疗作用。
目的初步探讨柴胡桂枝汤挥发油干预Fmrl基因敲除小鼠听源性惊厥的可能机制。
方法4周龄KO及WT小鼠按处理方式的不同被随机分为药物处理组(即腹腔注射柴胡桂枝汤挥发油)、溶媒AGS组、溶媒对照组和空白对照组,进一步将药物处理组和溶媒AGS组给予AGS诱发,溶媒对照组和空白对照组不给予AGS诱发；以高效液相色谱方法检测脑中氨基酸水平的变化,以免疫组织化学方法观察各组动物脑皮质及海马内GAD的表达；分别以邻苯三酚自氧化法、硫代巴比妥法、硝酸还原酶法检测各组小鼠脑内超氧化物歧化酶(SOD)、丙二醛(MDA)和一氧化氮(NO)的水平,以Golgi染色方法观察各组小鼠脑内树突棘形态变化,初步探讨柴胡桂枝汤挥发油改善KO小鼠AGS的可能机制。
结果KO小鼠脑皮质及海马内GAD阳性神经元数量与WT小鼠相比明显减少(P<0.05)。
KO溶媒对照组和KO空白对照组(未经AGS诱发)小鼠与WT溶媒对照组和和WT空白对照组相比,脑内Y-氨基丁酸及甘氨酸水平明显降低,谷氨酸水平明显升高(P<0.05)；KO溶媒对照组与KO空白对照组相比,脑内Y-氨基丁酸、甘氨酸,谷氨酸水平无明显变化；KO溶媒AGS组小鼠经AGS诱发后,与KO溶媒对照组和KO空白对照组相比,脑内γ-氨基丁酸水平有明显降低(P<0.05)；KO小鼠药物处理组与KO溶媒AGS组及WT用药组相比,脑内谷氨酸水平均有明显降低(P<0.05)。
与WT溶媒AGS对照小鼠相比,KO溶媒AGS组小鼠脑内SOD活力明显降低,MDA和NO水平则明显增高(P<0.05)；‘KO溶媒对照组与KO空白对照组脑内SOD、MDA和NO水平无明显变化,KO小鼠用药组注射柴胡桂枝汤挥发油后,与KO溶媒AGS组和WT用药照小鼠相比,SOD活力增高,而MDA和NO水平均降低(P<0.05)。
各组KO小鼠与各组WT小鼠脑皮质树突棘形态改变无统计学差异(P>0.05)。
结论柴胡桂枝汤挥发油可能通过降低兴奋性氨基酸水平,增加抑制性氨基酸水平,增强自由基清除,阻止过氧化物生成,减少NO神经毒性来治疗Fmr1基因敲除小鼠听源性惊厥。
Objective:To explore whether Fmrl mouse exhibits abnormal behavior as patients with Fragile X Syndrome (FXS).
Method:Genotypes of Fmrl knockout mice (KO mice) and wild type mice (WT mice) were identified by PCR and Western Blot in Experiment Animal Center of Guangzhou Medical College. The morphology of testis and dendritic spine of the two groups were studied under HE and Golgi stain. Animals were tested for audiogenic seizure (AGS), for learning capability and memory through Morris water maze, passive avoidance test, step-down test, and for general locomotor activity and willingness to explore via open field test, elevated plus maze and inner open field test.
Results:Genotype analysis revealed WT mice had the expected500bp DNA segments, whereas KO mice had800bp segments. What's more, KO mice exhibited macroochidism, abnormal morphology of dendritic spine and absent FMRP (Fragile X Mental Retardation Protein), and they were more susceptible to AGS (P<0.05). In the space navigation experiment of Morris water maze, they had longer latency and more platform-crossing activities than their WT counterparts (P<0.05); in space search experiment, KO mice stayed shorter than WT mice in the target quadrants (P<0.05). In passive avoidance test and step-down test, KO mice reacted swifter but made more mistakes (P<0.05). In open field test, they stayed longer in the central area and entered more constantly into the area than the WT mice (P<0.05); and in general, they traveled further and faster than WT mice (P<0.05). In elevated plus maze, they had longer duration, higher frequency and greater travel distance in the open area (P<0.05). In inner open field test, they traveled more often but stood less frequently (both P<0.05). Conclusion:Genotype, protein expression profile, morphological and behavioral aspects suggested that Fmrlgene knockout mice and patients of Fragile X syndrome behaved similarly, which are linked to the lost of FMRP expression. This study indicates that Fmrl KO mice can serve as animal model for FXS research.
Objective:To observe the effect of bupleuri and ramuli cinnamomi decoction on abnormal behaviours in Fmrl knockout mice.
Method:Bupleuri and ramuli cinnamomi decoction was extracted with supercritical carbon dioxide, whose components were assayed by GC-MS (Gas chromatography-mass spectrometry). Fmr1knockout (KO) and wild type (WT) mice of four-week old were randomized into three subgroups:treatment group (receiving intraperitoneal injection of bupleuri and ramuli cinnamomi decoction of different concentrations), solvent control group (receiving intraperitoneal injection of vegetable oil) and blank control group (receiving no injections). After treatments, animal behaviours were observed under open field test, elevated plus maze, inner open field test, step-down test, passive avoidance test and AGS test.
Results:GC-MS identified28components in bupleuri and ramuli cinnamomi decoction, whose main ingredients included gingerol (31.94%), eugenol (18.01%), monoterpenoids (12.34%),3-Butyl-1(3H)-isobenzofuranone (9.34%) and cinnamon substances (8.03%).
In open field test, the average speed, number of travels passing the central field and total traveling distance of KO and WT mice decreased with increased concentration of bupleuri and ramuli cinnamomi decoction. In elevated plus maze, travel duration, frequency and distance of KO treatment group in open arm decreased in comparison with KO solvent control group (P<0.05). In inner open field test, they moved less frequently but stood more often (P<0.05). In step-down test, their latency was prolonged and the number of errors was reduced (both P<0.05), whereas changes in those parameters were not significant among WT treatment group. In passive avoidance test, latency and errors extended and dwindled among KO treatment group (both P<0.05) but barely changed among WT mice (P>0.05). In audiogenic seizure experiment, latency delayed and severity of the seizure declined among KO treatment group with increased essential concentration (P<0.05) and seizure was suppressed under decoction of1.5mg/g. Conclusion:Bupleuri and ramuli cinnamomi decoction can be therapy to abnormal behaviour of KO mice by reducing audiogenic seizure and hyperactivity, and improving learning capability and memory.
Objective:To identify the intervention mechanisms of bupleuri and ramuli cinnamomi decoction on Fmrl knockout mouse.
Method:Experimental animals, KO and WT mice of four-week old, were randomized into three subgroups:treatment group (receiving intraperitoneal injection of bupleuri and ramuli cinnamomi decoction), solvent plus AGS group and solvent control group. Then, the first two groups underwent AGS induction whereas the third group was left untreated. We detected their levels of amino acid by high performance liquid chromatography and the expressions of GAD (glutamate decarboxylase) and other molecules in the hippocampus and cortex by immunohistochemistry. We assayed and compared the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) respectively by pyrogallol autoxidation method, thiobarbituric method and nitrate reductase method. These efforts would lead to possible mechanisms of bupleuri and ramuli cinnamomi decoction's therapeutic effect on abnormal behaviour of KO mice.
Results:KO mice possessed fewer neurons with GAD in the hippocampus and cortex than WT mice (P<0.05).
KO mice in solvent control group expressed fewer y-aminobutyric acid (GABA) and glycine but more glutamate than WT solvent control group (P<0.05). After AGS induction, KO mice of solvent plus AGS group had a significant decrease in GABA level as compared with KO blank control group (P<0.05). The glutamate level of KO treatment group was lower than KO solvent plus AGS group and WT treatment group (P<0.05).
SOD activity of KO solvent plus AGS group was lower but MDA and NO levels were higher than WT solvent plus AGS group (P<0.05). And KO treatment group manifested higher SOD activity and lower MDA and NO levels than KO solvent plus AGS and WT treatment groups (P<0.05).
bupleuri and ramuli cinnamomi decoction did not alter spine length after1time treatment in4W KO mice (p>0.05).
Conclusion:The intervention mechanisms of bupleuri and ramuli cinnamomi decoction on abnormal behaviours of Fmrl knockout mice may lie in the reduced ratio of excitatory amino acid to inhibitory amino acids, enhanced free radicals elimination, suppressed peroxide production and diminished NO neurotoxic effects.
方法以PCR和免疫印迹技术对Fmr1基因敲除(KO)小鼠和野生型(WT)小鼠进行基因型鉴定；HE和Go1gi染色方法分别观察2组动物睾丸和脑内树突棘形态；分别对实验动物进行听源性惊厥(AGS)观察,以水迷宫、避暗、跳台方法检测动物学习记忆水平,以旷场、高架十字迷宫和自主活动实验检测动物探索行为能力。
结果WT小鼠扩增出预期约为500bp的DNA片断,KO小鼠则是800bp的DNA片断,KO小鼠无FMRP蛋白表达,树突棘长度明显增长,密度显著增加,KO雄性小鼠有巨睾征；AGS易感性比WT明显增高(P<0.05)；Morris水迷宫实验的定向航行实验显示,KO小鼠的潜伏期和穿越平台次数与WT小鼠相比有明显增多(P<0.05)；空间搜索实验显示,KO小鼠在目标象限停留时间明显短于WT小鼠的停留时间(P<0.05)；避暗实验和跳台实验显示,KO小鼠潜伏期明显短于WT小鼠,而错误次数明显增多(P<0.05)；旷场实验显示,KO小鼠在中央区域停留时间及进入次数明显多于WT小鼠(P<0.05)；KO小鼠与WT小鼠相比,总运动路程明显增多,速度明显增快(P<0.05)；高架十字迷宫实验显示,KO小鼠在开放臂活动时间、次数以及路程均明显多于WT小鼠(P<0.05)；自主活动实验显示,KO小鼠的活动次数明显多于WT小鼠(P<0.05),而站立次数明显少于WT小鼠(P<0.05)。
结论从基因型、蛋白表达谱、形态学及行为学等方面结果提示Fmrl基因敲除小鼠具有人类脆性X综合征类似的表型,可作为FXS疾病模型用于论文的后续研究,而且这些表型与FMRP表达缺失有关。
目的观察柴胡桂枝汤挥发油对Fmr1基因敲除小鼠异常行为的干预。
方法利用超临界CO2萃取技术制备柴胡桂枝汤挥发油并用GC-MS分析鉴定柴胡桂枝汤挥发油成分；4周龄KO及WT小鼠按处理方式的不同被随机分为药物处理组(即腹腔注射柴胡桂枝汤挥发油)、溶媒对照组(即腹腔注射植物油)及空白对照组(即不给予任何处理)。药物处理组进一步按所给浓度的不同继续分组,分别对各组动物在给药后进行避暗、跳台、高架十字迷宫、旷场、自主活动和AGS等行为学观察。
结果经GC-MS分析鉴定柴胡桂枝汤挥发油含有28种组分。其中,最主要成分姜辣素占31.94%,丁香酚占18.01%,单萜类物质占12.34%,3-丁基-1(3H)-异苯并呋喃酮占9.34%,肉桂类物质占8.03%。
旷场实验显示,随柴胡桂枝汤挥发油浓度的增加,KO和WT小鼠的平均速度、穿越中央格次数、总路程等逐渐降低。高架十字迷宫实验显示,KO小鼠给予柴胡桂枝汤挥发油处理后,与KO溶媒组相比,KO小鼠在开放区域活动时间、次数以及路程均降低,有显著的统计学差异(P<0.05)。自主活动实验显示,使用柴胡桂枝汤挥发油后,KO小鼠的活动次数明显减少,动物站立次数明显增多(P<0.05)；跳台实验显示,柴胡桂枝汤挥发油处理后,KO小鼠潜伏期和错误次数有明显改善(P<0.05),WT小鼠潜伏期和错误次数有较少改善。避暗实验中,柴胡桂枝汤挥发油处理后,KO小鼠潜伏期延长(P<0.05),错误次数减少(P<0.05),WT小鼠潜伏期和错误次数无明显改善(P>0.05)。听源性惊厥实验中,随柴胡桂枝汤挥发油浓度的增加,KO小鼠的AGS的潜伏期延长,发作程度降低(P<0.05),1.5mg/g浓度的柴胡桂枝汤挥发油能完全抑制AGS的发生。
结论柴胡桂枝汤挥发油可以改善KO小鼠AGS和运动过多的发生,改善学习记忆能力,对KO小鼠的异常行为有一定治疗作用。
目的初步探讨柴胡桂枝汤挥发油干预Fmrl基因敲除小鼠听源性惊厥的可能机制。
方法4周龄KO及WT小鼠按处理方式的不同被随机分为药物处理组(即腹腔注射柴胡桂枝汤挥发油)、溶媒AGS组、溶媒对照组和空白对照组,进一步将药物处理组和溶媒AGS组给予AGS诱发,溶媒对照组和空白对照组不给予AGS诱发；以高效液相色谱方法检测脑中氨基酸水平的变化,以免疫组织化学方法观察各组动物脑皮质及海马内GAD的表达；分别以邻苯三酚自氧化法、硫代巴比妥法、硝酸还原酶法检测各组小鼠脑内超氧化物歧化酶(SOD)、丙二醛(MDA)和一氧化氮(NO)的水平,以Golgi染色方法观察各组小鼠脑内树突棘形态变化,初步探讨柴胡桂枝汤挥发油改善KO小鼠AGS的可能机制。
结果KO小鼠脑皮质及海马内GAD阳性神经元数量与WT小鼠相比明显减少(P<0.05)。
KO溶媒对照组和KO空白对照组(未经AGS诱发)小鼠与WT溶媒对照组和和WT空白对照组相比,脑内Y-氨基丁酸及甘氨酸水平明显降低,谷氨酸水平明显升高(P<0.05)；KO溶媒对照组与KO空白对照组相比,脑内Y-氨基丁酸、甘氨酸,谷氨酸水平无明显变化；KO溶媒AGS组小鼠经AGS诱发后,与KO溶媒对照组和KO空白对照组相比,脑内γ-氨基丁酸水平有明显降低(P<0.05)；KO小鼠药物处理组与KO溶媒AGS组及WT用药组相比,脑内谷氨酸水平均有明显降低(P<0.05)。
与WT溶媒AGS对照小鼠相比,KO溶媒AGS组小鼠脑内SOD活力明显降低,MDA和NO水平则明显增高(P<0.05)；‘KO溶媒对照组与KO空白对照组脑内SOD、MDA和NO水平无明显变化,KO小鼠用药组注射柴胡桂枝汤挥发油后,与KO溶媒AGS组和WT用药照小鼠相比,SOD活力增高,而MDA和NO水平均降低(P<0.05)。
各组KO小鼠与各组WT小鼠脑皮质树突棘形态改变无统计学差异(P>0.05)。
结论柴胡桂枝汤挥发油可能通过降低兴奋性氨基酸水平,增加抑制性氨基酸水平,增强自由基清除,阻止过氧化物生成,减少NO神经毒性来治疗Fmr1基因敲除小鼠听源性惊厥。
Objective:To explore whether Fmrl mouse exhibits abnormal behavior as patients with Fragile X Syndrome (FXS).
Method:Genotypes of Fmrl knockout mice (KO mice) and wild type mice (WT mice) were identified by PCR and Western Blot in Experiment Animal Center of Guangzhou Medical College. The morphology of testis and dendritic spine of the two groups were studied under HE and Golgi stain. Animals were tested for audiogenic seizure (AGS), for learning capability and memory through Morris water maze, passive avoidance test, step-down test, and for general locomotor activity and willingness to explore via open field test, elevated plus maze and inner open field test.
Results:Genotype analysis revealed WT mice had the expected500bp DNA segments, whereas KO mice had800bp segments. What's more, KO mice exhibited macroochidism, abnormal morphology of dendritic spine and absent FMRP (Fragile X Mental Retardation Protein), and they were more susceptible to AGS (P<0.05). In the space navigation experiment of Morris water maze, they had longer latency and more platform-crossing activities than their WT counterparts (P<0.05); in space search experiment, KO mice stayed shorter than WT mice in the target quadrants (P<0.05). In passive avoidance test and step-down test, KO mice reacted swifter but made more mistakes (P<0.05). In open field test, they stayed longer in the central area and entered more constantly into the area than the WT mice (P<0.05); and in general, they traveled further and faster than WT mice (P<0.05). In elevated plus maze, they had longer duration, higher frequency and greater travel distance in the open area (P<0.05). In inner open field test, they traveled more often but stood less frequently (both P<0.05). Conclusion:Genotype, protein expression profile, morphological and behavioral aspects suggested that Fmrlgene knockout mice and patients of Fragile X syndrome behaved similarly, which are linked to the lost of FMRP expression. This study indicates that Fmrl KO mice can serve as animal model for FXS research.
Objective:To observe the effect of bupleuri and ramuli cinnamomi decoction on abnormal behaviours in Fmrl knockout mice.
Method:Bupleuri and ramuli cinnamomi decoction was extracted with supercritical carbon dioxide, whose components were assayed by GC-MS (Gas chromatography-mass spectrometry). Fmr1knockout (KO) and wild type (WT) mice of four-week old were randomized into three subgroups:treatment group (receiving intraperitoneal injection of bupleuri and ramuli cinnamomi decoction of different concentrations), solvent control group (receiving intraperitoneal injection of vegetable oil) and blank control group (receiving no injections). After treatments, animal behaviours were observed under open field test, elevated plus maze, inner open field test, step-down test, passive avoidance test and AGS test.
Results:GC-MS identified28components in bupleuri and ramuli cinnamomi decoction, whose main ingredients included gingerol (31.94%), eugenol (18.01%), monoterpenoids (12.34%),3-Butyl-1(3H)-isobenzofuranone (9.34%) and cinnamon substances (8.03%).
In open field test, the average speed, number of travels passing the central field and total traveling distance of KO and WT mice decreased with increased concentration of bupleuri and ramuli cinnamomi decoction. In elevated plus maze, travel duration, frequency and distance of KO treatment group in open arm decreased in comparison with KO solvent control group (P<0.05). In inner open field test, they moved less frequently but stood more often (P<0.05). In step-down test, their latency was prolonged and the number of errors was reduced (both P<0.05), whereas changes in those parameters were not significant among WT treatment group. In passive avoidance test, latency and errors extended and dwindled among KO treatment group (both P<0.05) but barely changed among WT mice (P>0.05). In audiogenic seizure experiment, latency delayed and severity of the seizure declined among KO treatment group with increased essential concentration (P<0.05) and seizure was suppressed under decoction of1.5mg/g. Conclusion:Bupleuri and ramuli cinnamomi decoction can be therapy to abnormal behaviour of KO mice by reducing audiogenic seizure and hyperactivity, and improving learning capability and memory.
Objective:To identify the intervention mechanisms of bupleuri and ramuli cinnamomi decoction on Fmrl knockout mouse.
Method:Experimental animals, KO and WT mice of four-week old, were randomized into three subgroups:treatment group (receiving intraperitoneal injection of bupleuri and ramuli cinnamomi decoction), solvent plus AGS group and solvent control group. Then, the first two groups underwent AGS induction whereas the third group was left untreated. We detected their levels of amino acid by high performance liquid chromatography and the expressions of GAD (glutamate decarboxylase) and other molecules in the hippocampus and cortex by immunohistochemistry. We assayed and compared the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) respectively by pyrogallol autoxidation method, thiobarbituric method and nitrate reductase method. These efforts would lead to possible mechanisms of bupleuri and ramuli cinnamomi decoction's therapeutic effect on abnormal behaviour of KO mice.
Results:KO mice possessed fewer neurons with GAD in the hippocampus and cortex than WT mice (P<0.05).
KO mice in solvent control group expressed fewer y-aminobutyric acid (GABA) and glycine but more glutamate than WT solvent control group (P<0.05). After AGS induction, KO mice of solvent plus AGS group had a significant decrease in GABA level as compared with KO blank control group (P<0.05). The glutamate level of KO treatment group was lower than KO solvent plus AGS group and WT treatment group (P<0.05).
SOD activity of KO solvent plus AGS group was lower but MDA and NO levels were higher than WT solvent plus AGS group (P<0.05). And KO treatment group manifested higher SOD activity and lower MDA and NO levels than KO solvent plus AGS and WT treatment groups (P<0.05).
bupleuri and ramuli cinnamomi decoction did not alter spine length after1time treatment in4W KO mice (p>0.05).
Conclusion:The intervention mechanisms of bupleuri and ramuli cinnamomi decoction on abnormal behaviours of Fmrl knockout mice may lie in the reduced ratio of excitatory amino acid to inhibitory amino acids, enhanced free radicals elimination, suppressed peroxide production and diminished NO neurotoxic effects.
引文
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