Rongzong Qiu1, Weifeng Yao2, Haocong Ji3, Dongdong Yuan4, Xiaofeng Gao3, Weiping Sha3, Fei Wang3, Pinjie Huang3, Ziqing Hei5. 1. Department of Anesthesiology, Huizhou First Hospital, Huizhou, Guangdong 516000, China; Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China. 2. Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China. Electronic address: yaowf3@mail.sysu.edu.cn. 3. Department of Anesthesiology, Huizhou First Hospital, Huizhou, Guangdong 516000, China. 4. Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China. 5. Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China. Electronic address: heizq@mail.sysu.edu.cn.
Abstract
BACKGROUND: Acute kidney injury occurred after sepsis, resulting in high mortality. This research aims to elucidate the mechanistic effect of DEX on the renal inflammation resolution during sepsis in rats. METHODS: The rats were randomly divided into a sham group and the other three cecal ligation and puncture (CLP) model groups, based on different treatments: placebo, DEX and 2-adrenergic receptor (AR) inhibitor atipamezole (AT) treatment (DEX + AT) groups. The survival of septic rats within 24 h was recorded. Tissue pathology, plasma IL-1β, IL-6, TNF-α, lipoxygenase-5 and lipoxin A4 were evaluated. Western blotting and immunostaining was used to determine expression of TLR4, IκB, IKK, NF-κB p65 and pp65 in kidney tissue. Then qPCR was used to analyze the mRNA expression of renal α2A-AR, α2B-AR and α2C-AR. RESULTS: Rat mortality and kidney inflammation were significantly increased in septic rats. Specifically, IL-1β, IL-6 and TNF-α plasma levels, NF-κB activity, and TLR4 expression in rat kidney tissues were increased after CLP. In the DEX treatment group, mortality was reduced, histology changes were minor, and lipoxygenase-5, and lipoxin A4 expression were increased. The expression of IL-1β, IL-6 and TNF-α, NF-κB activity and TLR4 expression in rat kidney tissues were also decreased. These results indicated that DEX treatment alleviates acute kidney injury induced by CLP. However, the effects of DEX were apparently suppressed by atipamezole in the DEX + AT group. CONCLUSION: The current study demonstrated the protective effect of DEX on CLP-induced kidney injury, which may be effective by attenuating NF-κB pathway activation with lipoxin A4.
BACKGROUND:Acute kidney injury occurred after sepsis, resulting in high mortality. This research aims to elucidate the mechanistic effect of DEX on the renal inflammation resolution during sepsis in rats. METHODS: The rats were randomly divided into a sham group and the other three cecal ligation and puncture (CLP) model groups, based on different treatments: placebo, DEX and 2-adrenergic receptor (AR) inhibitor atipamezole (AT) treatment (DEX + AT) groups. The survival of septic rats within 24 h was recorded. Tissue pathology, plasma IL-1β, IL-6, TNF-α, lipoxygenase-5 and lipoxin A4 were evaluated. Western blotting and immunostaining was used to determine expression of TLR4, IκB, IKK, NF-κB p65 and pp65 in kidney tissue. Then qPCR was used to analyze the mRNA expression of renal α2A-AR, α2B-AR and α2C-AR. RESULTS:Rat mortality and kidney inflammation were significantly increased in septic rats. Specifically, IL-1β, IL-6 and TNF-α plasma levels, NF-κB activity, and TLR4 expression in rat kidney tissues were increased after CLP. In the DEX treatment group, mortality was reduced, histology changes were minor, and lipoxygenase-5, and lipoxin A4 expression were increased. The expression of IL-1β, IL-6 and TNF-α, NF-κB activity and TLR4 expression in rat kidney tissues were also decreased. These results indicated that DEX treatment alleviates acute kidney injury induced by CLP. However, the effects of DEX were apparently suppressed by atipamezole in the DEX + AT group. CONCLUSION: The current study demonstrated the protective effect of DEX on CLP-induced kidney injury, which may be effective by attenuating NF-κB pathway activation with lipoxin A4.