未经证实:短肠综合征(SBS)具有很高的发病率和死亡率,促进残余肠的肠适应是关键的治疗方法。膳食肌醇六磷酸(IP6)在维持肠道稳态、但其对SBS的影响尚不清楚。本研究旨在研究IP6对SBS的影响并阐明其潜在机制。
UNASSIGNED:将40只雄性SD大鼠(3周龄)随机分为四组(假,Sham+IP6,SBS,和SBS+IP6组)。给大鼠喂食标准的颗粒状大鼠食物,并在适应1周后切除75%的小肠。他们每天通过管饲法接受1mLIP6处理(2mg/g)或无菌水,持续13天。肠道长度,肌醇1,4,5-三磷酸(IP3)的水平,组蛋白脱乙酰酶3(HDAC3)活性,检测肠上皮细胞-6(IEC-6)的增殖。
UNASSIGNED:IP6处理增加了SBS大鼠的残余肠长度。此外,IP6治疗导致体重增加,肠粘膜重量,和IEC扩散,肠道通透性降低.IP6治疗导致粪便和血清中IP3水平较高,和肠道的HDAC3活性较高。有趣的是,HDAC3活性与粪便(r=0.49,P=0.01)和血清(r=0.44,P=0.03)中IP3水平呈正相关。始终如一,IP3处理通过增加体外HDAC3活性促进IEC-6细胞的增殖。IP3调节叉头盒O3(FOXO3)/细胞周期蛋白D1(CCND1)信号通路。
UNASSIGNED:IP6治疗可促进SBS大鼠的肠道适应。IP6代谢为IP3以增加HDAC3活性以调节FOXO3/CCND1信号通路,并且可能代表SBS患者的潜在治疗方法。
UNASSIGNED: Short bowel syndrome (SBS) has high morbidity and mortality rates, and promoting intestinal adaptation of the residual intestine is a critical treatment. Dietary inositol hexaphosphate (IP6) plays an important role in maintaining intestinal homeostasis, but its effect on SBS remains unclear. This study aimed at investigating the effect of IP6 on SBS and clarified its underlying mechanism.
UNASSIGNED: Forty male Sprague-Dawley rats (3-week-old) were randomly assigned into four groups (Sham, Sham + IP6, SBS, and SBS + IP6 groups). Rats were fed standard pelleted rat chow and underwent resection of 75% of the small intestine after 1 week of acclimation. They received 1 mL IP6 treatment (2 mg/g) or sterile water daily for 13 days by gavage. Intestinal length, levels of inositol 1,4,5-trisphosphate (IP3), histone deacetylase 3 (HDAC3) activity, and proliferation of intestinal epithelial cell-6 (IEC-6) were detected.
UNASSIGNED: IP6 treatment increased the length of the residual intestine in rats with SBS. Furthermore, IP6 treatment caused an increase in body weight, intestinal mucosal weight, and IEC proliferation, and a decrease in intestinal permeability. IP6 treatment led to higher levels of IP3 in feces and serum, and higher HDAC3 activity of the intestine. Interestingly, HDAC3 activity was positively correlated with the levels of IP3 in feces (r = 0.49, P = 0.01) and serum (r = 0.44, P = 0.03). Consistently, IP3 treatment promoted the proliferation of IEC-6 cells by increasing HDAC3 activity in vitro. IP3 regulated the Forkhead box O3 (FOXO3)/Cyclin D1 (CCND1) signaling pathway.
UNASSIGNED: IP6 treatment promotes intestinal adaptation in rats with SBS. IP6 is metabolized to IP3 to increase HDAC3 activity to regulate the FOXO3/CCND1 signaling pathway and may represent a potential therapeutic approach for patients with SBS.