Ghrelin 通过 Tim-3 介导的 HMGB1/NF-κB 通路抑制蛛网膜下腔出血后的早期脑损伤。
Ghrelin inhibits early brain injury due to subarachnoid hemorrhage via the Tim-3-mediated HMGB1/NF-κB pathway.
机构信息
Department of Neurology, Yantaishan Hospital, Yantai, Shandong Province, China.
Department of Neurology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, China.
出版信息
J Chem Neuroanat. 2022 Oct;124:102138. doi: 10.1016/j.jchemneu.2022.102138. Epub 2022 Jul 19.
OBJECTIVE
To explore the protective effect of Ghrelin on EBI caused by SAH through the HMGB1/NF-κB pathway mediated by Tim-3.
METHODS
Rats were divided into four groups (n = 6): Sham group (Sham), SAH+vehicle group (SAH), SAH + 0.02 μg/kg rhGhrelin group (rhGhrelin-L), SAH + 0.04 μg/kg rhGhrelin group (rhGhrelin-H). At 48 h after SAH, the behavioral impairment in rats was examined for using neurobehavioral scores. The pathological change in the temporal basal brain tissue was observed by HE, and the expression of GHSR-1α and Tim-3 in the temporal basal brain tissue was observed by Western blot. To further validate that rhGhrelin could inhibit SAH-induced EBI by the Tim-3-mediated HMGB1/NF-κB pathway, we treated rats with the AAV-Tim-3. The contents of the inflammatory factors IL-1β, TNF-α, IL-6 was determined by ELISA, apoptosis was detected by TUNEL, the neurons were visualized by Nissl staining, the expression of GHSR-1α，Tim-3, HMGB1, RAGE, NF-κB p65 was determined by Western blot.
RESULTS
Compared with the SAH group, rats treated with rhGhrelin had a significantly lower neurobehavioral score, significantly decreased inflammatory factors IL-1β, TNF-α, IL-6 expression, significantly decreased apoptosis index, and significantly decreased Tim-3, HMGB1, RAGE, NF-κB p65 expression(p < 0.01). The protective effect of rhGhrelin on the SAH-induced EBI was reversed by the AAV-Tim-3.
CONCLUSION
Ghrelin has beneficial effects against SAH-induced EBI by inhibiting the HMGB1/NF-κB pathway, which may be regulated by Tim-3.
目的
通过 Tim-3 介导的 HMGB1/NF-κB 通路探讨 Ghrelin 对蛛网膜下腔出血（SAH）引起的 EBI 的保护作用。
方法
将大鼠分为四组（n=6）：假手术组（Sham）、SAH+vehicle 组（SAH）、SAH+0.02μg/kg rhGhrelin 组（rhGhrelin-L）、SAH+0.04μg/kg rhGhrelin 组（rhGhrelin-H）。SAH 后 48 h，采用神经行为学评分检测大鼠的行为损伤；通过 HE 观察颞基底脑组织的病理变化，通过 Western blot 观察颞基底脑组织中 GHSR-1α 和 Tim-3 的表达。为进一步验证 rhGhrelin 可通过 Tim-3 介导的 HMGB1/NF-κB 通路抑制 SAH 诱导的 EBI，我们用 AAV-Tim-3 处理大鼠。通过 ELISA 测定炎症因子 IL-1β、TNF-α、IL-6 的含量，通过 TUNEL 检测细胞凋亡，通过 Nissl 染色观察神经元，通过 Western blot 测定 GHSR-1α、Tim-3、HMGB1、RAGE、NF-κB p65 的表达。
结果
与 SAH 组相比，rhGhrelin 处理组大鼠的神经行为评分显著降低，炎症因子 IL-1β、TNF-α、IL-6 的表达显著降低，细胞凋亡指数显著降低，Tim-3、HMGB1、RAGE、NF-κB p65 的表达显著降低（p<0.01）。AAV-Tim-3 逆转了 rhGhrelin 对 SAH 诱导的 EBI 的保护作用。
结论
Ghrelin 通过抑制 HMGB1/NF-κB 通路对 SAH 诱导的 EBI 发挥有益作用，该作用可能通过 Tim-3 调节。
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