Background

Ischemia-reperfusion injury (IRI) poses a significant challenge to liver transplantation (LT). The underlying mechanism primarily involves overactivation of the immune system. Heat shock protein 110 (HSP110) functions as a molecular chaperone that helps stabilize protein structures.

Methods

An IRI model was established by performing LT on Sprague-Dawley rats, and HSP110 was silenced using siRNA. Hematoxylin-eosin staining, TUNEL, immunohistochemistry, ELISA and liver enzyme analysis were performed to assess IRI following LT. Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.

Results

Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT (P < 0.05). However, when rats were injected with siRNA-HSP110, IRI subsequent to LT was notably reduced (P < 0.05). Additionally, the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced (P < 0.05). Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver (P < 0.05).

Conclusions

HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells. Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

中文翻译：

---

HSP110通过促进NF-κB通路加重肝移植术后缺血再灌注损伤

背景

缺血再灌注损伤（IRI）对肝移植（LT）提出了重大挑战。潜在的机制主要涉及免疫系统的过度激活。热休克蛋白 110 (HSP110) 作为分子伴侣，有助于稳定蛋白质结构。

方法

通过对 Sprague-Dawley 大鼠进行 LT 建立 IRI 模型，并使用 siRNA 沉默 HSP110。进行苏木精-伊红染色、TUNEL、免疫组织化学、ELISA 和肝酶分析以评估 LT 后的 IRI。进行蛋白质印迹和定量逆转录聚合酶链反应来研究相关的分子变化。

结果

我们的研究结果表明，LT 后大鼠肝脏中 HSP110 的 mRNA 和蛋白水平表达均显着增加（P < 0.05）。然而，当大鼠注射siRNA-HSP110时，LT后的IRI显着降低（P <0.05）。此外，大鼠血清中肝酶和炎症趋化因子水平显着降低（P < 0.05）。siRNA 沉默 HSP110 后，肝脏 Kupffer 细胞 M1 型极化显着降低，肝脏 NF-κB 通路下调（P < 0.05）。

结论

肝脏中的 HSP110 通过激活 NF-κB 通路并诱导 Kupffer 细胞的 M1 型极化，促进大鼠 LT 后的 IRI。以 HSP110 为靶点来预防 LT 后的 IRI 可能是治疗 LT 相关 IRI 的一种有前景的新方法。