Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A.
Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A.
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纳米小白菊内酯通过 5-HTR2A 抑制细胞凋亡和 ROS，改善脓毒症的肠道屏障功能。
DOI：
10.2147/ijn.s394544
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发表时间：
2023
影响因子：
8
通讯作者：
中科院分区：
文献类型：
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肠屏障功能障碍是脓毒症的重要并发症，但治疗方法有限。近年来，小白菊素（PTL）作为脓毒症的治疗策略引起了广泛关注，但纳米小白菊素（Nano PTL）是否能治疗脓毒症引起的肠屏障功能障碍尚不清楚。本研究采用盲肠结扎穿孔（CLP）诱导的脓毒症大鼠模型和脂多糖（LPS）刺激的肠上皮细胞（IEC）模型，探讨PTL对肠屏障功能障碍的影响。同时，我们合成了纳米PTL，并比较了纳米PTL和普通PTL对脓毒症大鼠肠屏障功能和肠上皮细胞的保护作用。采用网络药理学和5-羟色胺2A（5-HTR2A）抑制剂研究PTL对脓毒症肠屏障功能的影响。纳米PTL的包封率为95 ± 1.5%，载药量为11 ± 0.5%，肠上皮细胞的平均摄取率为94%。普通PTL和纳米PTL在体内均能提高脓毒症大鼠的存活率和存活时间，降低平均动脉压和血清炎性细胞因子水平，保护肝肾功能;在体外均能通过5-HTR2A提高跨膜阻力（TEER）值，降低活性氧（ROS）和细胞凋亡。纳米PTL的效果优于普通PTL。普通PTL和纳米PTL均能通过上调5-HTR2A抑制细胞凋亡和活性氧来保护脓毒症大鼠肠屏障功能，纳米PTL优于普通PTL。
Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured. In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis. The encapsulation rate of Nano PTL was 95±1.5%, the drug loading rate was 11±0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL. Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.