Effects of gadolinium chloride inhibition of liver Kupffer cells on intestinal mechanical barrier function following cecal ligation and puncture-induced sepsis in rats

Objective: The classical "gut liver axis" theory expounds the relationship among intestinal barrier function, liver Kupffer cells, and systemic inflammatory response. The inflammatory response is closely related to the development and occurrence of sepsis. In this study, we investigated whether inhibition of Kupffer cells by gadolinium chloride (GdCl3) can alleviate the systemic inflammatory response, thereby protecting the intestinal mucosal barrier function. Methods: In this study, sepsis was modeled by cecal ligation and puncture (CLP). Sprague-Dawley (SD) rats were randomly divided into four groups: Sham operation group, GdCl3 pretreatment sham operation group, CLP group, and GdCl3 pretreatment group. Rats in the two pretreatment groups were administered 5, 10, 20, or 40 mg/kg GdCl3, respectively. Blood and intestinal tissue samples were taken from each group for biochemical and histopathological analyses. Results: The results showed that the pretreatment with 5 mg/kg GdCl3 could improve the inflammatory response, intestinal tight junction protein expression, and intestinal tissue apoptosis in septic rats, although the effect was not obvious. With increasing dose, a relatively stable dose range appeared, with 10 and 20 mg/kg pretreatments showing no significant difference with regards to the reduction of intestinal damage in septic rats. However, when the dose reached 40 mg/kg we observed aggravated intestinal damage. Conclusions: The inhibition of Kupffer cells by GdCl3 had a protective effect on intestinal barrier function, which may be related to the reduction of inflammatory factors secreted by Kupffer cells. Moreover, this protective effect was GdCl3 dose-dependent.