白藜芦醇对创伤性颅脑损伤大鼠的肠道菌群和PI3K/Akt信号通路调节的作用机制
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广西医疗卫生适宜技术开发与推广应用项目(S2024099)


Study on the mechanism of resveratrol in regulating the intestinal flora and PI3K/Akt signaling pathway in rats with traumatic craniocerebral injury
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    摘要:

    目的 基于肠脑轴探讨白藜芦醇(RES)对创伤性颅脑损伤(TBI)大鼠PI3K/Akt信号通路的调节及神经功能、肠道菌群的影响。方法 SPF级SD大鼠30只,随机分为Sham组、TBI组和RES组,每组10只,改良自由落体法创建TBI大鼠模型,RES灌胃干预后观察大鼠神经功能评分,水迷宫实验评估神经功能恢复情况,HE 染色观察脑组织及结肠组织病理学变化,ELISA 法检测大鼠血清 TNF-α、IL-6、脂多糖(LPS)含量,Western blot 法检测 PI3K、Akt、 TNF-α、IL-6的蛋白表达水平,16 s rDNA 基因测序观察各组小鼠肠道菌群多样性、种属变化。结果 与TBI组比较,RES干预后大鼠第7天神经功能评分开始降低,第14天神经功能评分显著降低(P<0.05) 。Morris水迷宫定位航行期第3、4天,TBI组较Sham组的平台潜伏期、总路程延长(P<0.05);与TBI组相比,RES组的平台潜伏期、总路程均有缩短(P<0.05)。在空间探索期中,TBI组穿台次数较Sham组减少,目标象限路程占比减小(P<0.05);与TBI组比较,RES组在第6天穿台次数出现显著差异(P<0.05),目标象限路程占比增大(P<0.05)。RES组较TBI组的病理结果提示神经元损伤减轻。RES组较TBI组血清TNF-α、IL-6、LPS浓度降低(P<0.05) ,海马组织中TNF-α、IL6表达量下降,PI3K、Akt表达量升高(P<0.05)。TBI组大鼠菌群多样性降低,RES干预后厚壁菌门 (Firmicutes)、颤螺菌属 (Oscillospira)等菌群的相对丰度升高;白藜芦醇可丰富菌群多样性,使乳酸杆菌属等相对丰度增加。结论 白藜芦醇通过增加肠道有益菌,降低致病菌,丰富菌群多样性,抑制炎症因子生成以及调控PI3K/Akt通路改善创伤性颅脑损伤的神经功能恢复

    Abstract:

    Objective To investigate the regulation of the PI3K/Akt signaling pathway and its effects on neurological function and intestinal flora in rats with traumatic craniocerebral injury. Methods Thirty SPF-grade SD rats were randomly divided into the Sham group, the TBI group and the RES group, with 10 rats in each group. The TBI rat model was established by the modified free fall method. The neurological function score of the rats was observed after RES intragastric administration intervention. The recovery of neurological function was evaluated by the water maze test. The histopathological changes of brain tissue and colon tissue were observed by HE staining. The contents of TNF-α, IL6 and LPS in rat serum were detected by ELISA. The protein expression levels of PI3K, Akt, TNF-α and IL-6 were detected by Western blot. The diversity of intestinal flora and species changes of mice in each group were observed by 16s rDNA gene sequencing. Results Compared with the TBI group, the neurological function score in the RES group began to decrease on the 7th day and significantly decreased on the 14th day (P<0.05). On the 3rd and 4th days of the Morris water maze positioning voyage, the platform latency and total distance of the TBI group were prolonged compared with those of the Sham group (P<0.05). Compared with the TBI group, the escape latency and total distance in the RES group were both shortened (P<0.05). During the space exploration period, the number of times the TBI group crossed the platform was less than that of the Sham group, and the proportion of the distance in the target quadrant decreased (P<0.05). Compared with the TBI group, there was a significant difference in the number of platform passes in the RES group on the 6th day (P< 0.05), and the proportion of distance in the target quadrant increased (P<0.05). The pathological results of the RES group compared with the TBI group indicated that neuronal injury was alleviated, the concentrations of serum TNF-α, IL-6 and LPS decreased (P<0.05), the expression levels of TNF-α and IL6 in hippocampal tissue decreased, and the expression levels of PI3K and Akt increased (P<0.05). The diversity of the microbiota in the TBI group of rats decreased, and the relative abundance of microbiota such as Firmicutes and Oscillospira increased after RES intervention. Resveratrol could enrich the diversity of the flora and increase the relative abundance of genera such as Lactobacillus.Conclusion Resveratrol improves the neurological function recovery of traumatic brain injury by increasing beneficial intestinal bacteria, reducing pathogenic bacteria, enriching the diversity of the microbiota, inhibiting the generation of inflammatory factors, and regulating the PI3K/Akt pathway

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  • 在线发布日期: 2026-06-18
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