Protective effects of panax notoginseng saponin on dextran sulfate sodium-induced colitis in rats through phosphoinositide-3-kinase protein kinase B signaling pathway inhibition
Protective effects of panax notoginseng saponin on dextran sulfate sodium-induced colitis in rats through phosphoinositide-3-kinase protein kinase B signaling pathway inhibition
复制标题
三七总皂苷通过抑制磷酸肌醇3-激酶蛋白激酶B信号通路对右旋糖酐硫酸钠诱导的大鼠结肠炎的保护作用
DOI：
10.3748/wjg.v26.i11.1156
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发表时间：
2020-03-21
影响因子：
4.3
通讯作者：
Yan, Xin
中科院分区：
文献类型：
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作者：
Lu, Qing-Ge;Zeng, Li;Yan, Xin
背景肠道炎症是一种常见的消化道疾病，治疗多采用激素类药物。激素类药物在一定程度上是有效的，但长期使用可能会带来许多并发症。目的探讨三七总皂苷（PNS）通过抑制磷脂酰肌醇-3-激酶蛋白激酶B（PI 3 K/AKT）信号通路对葡聚糖硫酸钠（DSS）诱导的大鼠肠道炎症损伤的保护作用。方法采用DSS诱导大鼠结肠炎模型，分为对照组（不造模）、DSS组、DSS + PNS 50 mg/kg组、DSS + PNS 100 mg/kg组。检测各组大鼠肠组织损伤、氧化应激指标、炎症指标、紧密连接蛋白、细胞凋亡、巨噬细胞极化及TLR 4/AKT信号通路。用PI 3 K/AKT信号通路抑制剂LY 294002阻断大鼠结肠组织中的PI 3 K/AKT信号通路。结果与对照组相比，DSS组大鼠结肠长度明显缩短，疾病活动指数、氧化应激反应和炎症指数明显增加，紧密连接相关蛋白表达明显减少。此外，DSS组显示凋亡细胞数量显著增加，并显示脾和结肠组织中M1巨噬细胞显著增加。结肠组织中M2巨噬细胞数量显著减少，PI 3 K/AKT信号通路激活（均P < 0.05）。与DSS组相比，DSS + PNS组大鼠结肠长度明显延长，疾病活动指数明显降低，氧化应激反应和炎症反应明显减轻。此外，该组显示紧密连接相关蛋白的表达显着增加，凋亡细胞数量显着减少，脾脏和结肠组织中的M1巨噬细胞显着减少。该组进一步显示结肠组织中M2巨噬细胞显著增加，并且显著抑制PI 3 K/AKT信号通路的激活，以及剂量依赖性（均P < 0.05）。当PI 3 K/AKT信号通路受到抑制时，DSS + LY 294002组结肠组织细胞凋亡率明显低于DSS组（P < 0.05）。结论三七总皂苷通过抑制PI 3 K/AKT信号通路对DSS诱导的大鼠肠道炎症损伤具有保护作用，有望成为治疗结肠炎的药物。
BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many complications. AIM To explore the protective effects of panax notoginseng saponin (PNS) against dextran sulfate sodium (DSS)-induced intestinal inflammatory injury through phosphoinositide-3-kinase protein kinase B (PI3K/AKT) signaling pathway inhibition in rats. METHODS Colitis rat models were generated via DSS induction, and rats were divided into control (no modeling), DSS, DSS + PNS 50 mg/k, and DSS + PNS 100 mg/kg groups. Then, the intestinal injury, oxidative stress parameters, inflammatory indices, tight junction proteins, apoptosis, macrophage polarization, and TLR4/AKT signaling pathway in colon tissues from rats in each of the groups were detected. The PI3K/AKT signaling pathway in the colon tissue of rats was blocked using the PI3K/AKT signaling pathway inhibitor, LY294002. RESULTS Compared with rats in the control group, rats in the DSS group showed significantly shortened colon lengths, and significantly increased disease activity indices, oxidative stress reactions and inflammatory indices, as well as significantly decreased expression of tight junction-associated proteins. In addition, the DSS group showed significantly increased apoptotic cell numbers, and showed significantly increased M1 macrophages in spleen and colon tissues. They also showed significantly decreased M2 macrophages in colon tissues, as well as activation of the PI3K/AKT signaling pathway (all P < 0.05). Compared with rats in the DSS group, rats in the DSS + PNS group showed significantly lengthened colon lengths, decreased disease activity indices, and significantly alleviated oxidative stress reactions and inflammatory responses. In addition, this group showed significantly increased expression of tight junction-associated proteins, significantly decreased apoptotic cell numbers, and significantly decreased M1 macrophages in spleen and colon tissues. This group further showed significantly increased M2 macrophages in colon tissues, and significantly suppressed activation of the PI3K/AKT signaling pathway, as well as a dose dependency (all P < 0.05). When the PI3K/AKT signaling pathway was inhibited, the apoptosis rate of colon tissue cells in the DSS + LY294002 group was significantly lower than that of the DSS group (P < 0.05). CONCLUSION PNS can protect rats against DSS-induced intestinal inflammatory injury by inhibiting the PI3K/AKT signaling pathway, and therefore may be potentially used in the future as a drug for colitis.