Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.
Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.
Drug Des Devel Ther. 2023 Jul 25;17:2183-2192. doi: 10.2147/DDDT.S403087. eCollection 2023.
Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of GG (LGG) in relieving intestinal mucosal injury induced by TMZ.
Glioblastoma mice were divided into four groups: CON (control), LGG (10 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1β, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKβ, IκBα, and P65 with their phosphorylation in jejunum were measured.
Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos-IKKβ and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group.
LGG inhibits the activation of the TLR4-NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.
替莫唑胺（TMZ）可诱导肠道黏膜损伤，支持治疗无法完全逆转这种损伤。益生菌可调节肠道微生物组成和宿主免疫系统，从而可能缓解这种副作用。本研究旨在探讨 GG（LGG）缓解 TMZ 诱导的肠道黏膜损伤的潜力及其机制。
将脑胶质瘤小鼠分为 4 组：CON（对照组）、LGG（10CFU/mL，治疗 7 天）、TMZ（50mg/kg·d，治疗 5 天）、LGG+TMZ（LGG 治疗 7 天，随后 TMZ 治疗 5 天）。记录体重、摄食量和粪便 pH 值。TMZ 治疗结束后 1 天采集肠道组织样本。测定肠道损伤程度、空肠中 IL1β、IL6、TNFα 和 IL10 的表达。测定空肠中紧密连接蛋白（ZO1、occludin）、TLR4、IKKβ、IκBα 和 P65 及其磷酸化水平。
与 TMZ 组相比，LGG+TMZ 组的体重减轻、摄食量减少和脾脏指数下降均得到缓解，肠道缩短和空肠绒毛损伤程度也得到缓解。LGG+TMZ 组的紧密连接蛋白表达明显高于 TMZ 组。TMZ 组肠组织中 IκBα 明显减少，phos-IKKβ 和 phos-P65 与 CON 组相比增加，LGG 逆转了 LGG+TMZ 组中 IκBα 和 phos-P65 的变化。TMZ 组肠道炎症细胞因子明显增加，而 LGG+TMZ 组则较低。此外，LGG 组 TLR4 的表达明显低于 CON 组。与 TMZ 组相比，LGG+TMZ 组 LGG 抑制了 TLR4 在 TMZ 后的升高。
LGG 抑制 TLR4-NFκB 通路的激活，缓解 TMZ 诱导的肠道黏膜炎症，从而保护空肠绒毛和黏膜物理屏障。
