4,4′-二异硫氰基芪-2,2′-二磺酸对脓毒症小鼠心肌炎性反应的作用及机制

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Abstract Objective To investigate the effect and mechanism of 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) on myocardial inflammatory response in sepsis mice. Methods A total of 52 male BALB/c mice were divided into 4 groups by random number table method, namely blank control group, lipopolysaccharide (LPS) group, low dose DIDS group and high dose DIDS group, with 13 mice in each group. For 3 days of pretreatment, the low dose DIDS group and the high dose DIDS group were intraperitoneally injected with 7 and 14 mg/kg DIDS every day, respectively, while the blank control group and the LPS group were given the same amount of phosphate buffer salt solution (PBS) intraperitoneally every day. After 2 h of pretreatment on the third day, PBS was injected intraperitoneally into the blank control group, and LPS 10 mg/kg was injected intraperitoneally into the other three groups to establish a mouse sepsis model. After the model was created successfully, the survival status of 10 mice in each group were observed for 48 h, and the survival rates were calculated. In addition, 3 mice in each group were sacrificed after 4 h, and their heart tissues were taken. The mRNA expression of inflammatory factors [including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6)] and genes related to Notch signaling pathway (including Notch1-4, Dll1 and Jag1) were detected by real-time PCR. Western blot was used to detect the expression of proteins related to the Notch signaling pathway. Results Compared with the LPS group, the survival rate of mice in the high dose DIDS group was significantly improved, with a highly statistically significant difference (P < 0.01). Compared with the blank control group, the mRNA levels of TNF-α,IL-1β and IL-6 in the LPS group were significantly increased, with statistically significant differences (all P ＜ 0.05). Compared with the LPS group, the mRNA levels of TNF-α，IL-1β and IL-6 in the high dose DIDS group were significantly decreased, with statistically significant differences (all P ＜ 0.05). Compared with the LPS group, mRNA expression levels of Notch1, Notch3, Dll 1 and Jag 1 of Notch signaling related genes in the high-dose DIDS group were increased, and protein levels of Dll 1 and Jag 1 were increased, with statistically significant differences (all P < 0.05). Conclusion DIDS can significantly reduce the myocardial inflammatory response in sepsis mice, and its mechanism may be related to the regulation of Notch signaling pathway.

Key words： 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid Inflammation Sepsis Notch signaling pathway

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	WANG Yan1 XIA Lin2 CAI Huazhong3 XIONG Yuyun2

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WANG Yan1 XIA Lin2 CAI Huazhong3 XIONG Yuyun2. Effect and mechanism of 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid on myocardial inflammatory response in sepsis mice[J]. 中国医药导报, 2020, 17(3): 4-7,21.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2020/V17/I3/4

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