Ait-Belgnaoui A, Han W, Lamine F, Eutamene H, Fioramonti J, Bueno L, Theodorou V
Neuro-Gastroenterology and Nutrition Unit, UMR 1054 INRA/ESAP, Toulouse, France.
Gut. 2006 Aug;55(8):1090-4. doi: 10.1136/gut.2005.084194. Epub 2006 Feb 28.
Stress induced increase in colonic paracellular permeability results from epithelial cell cytoskeleton contraction and is responsible for stress induced hypersensitivity to colorectal distension (CRD). The probiotic Lactobacillus farciminis releases spontaneously nitric oxide (NO) in the colonic lumen in vivo and exerts anti-inflammatory effects. This study aimed: (i) to evaluate the effects of L farciminis on stress induced hypersensitivity to CRD and increase in colonic paracellular permeability; and (ii) to ascertain whether these effects are NO mediated and related to changes in colonocyte myosin light chain phosphorylation (p-MLC).
Female Wistar rats received either 10(11) CFU/day of L farciminis or saline orally over 15 days before partial restraint stress (PRS) or sham-PRS application. Visceral sensitivity to CRD and colonic paracellular permeability was assessed after PRS or sham-PRS. Haemoglobin was used as an NO scavenger. Western blotting for MLC kinase, MLC, and p-MLC were performed in colonic mucosa from L farciminis treated and control rats after PRS or sham-PRS.
PRS significantly increased the number of spike bursts for CRD pressures of 30-60 mm Hg as well as colonic paracellular permeability. L farciminis treatment prevented both effects, while haemoglobin reversed the protective effects of L farciminis. p-MLC expression increased significantly from 15 to 45 minutes after PRS, and L farciminis treatment prevented this increase.
L farciminis treatment prevents stress induced hypersensitivity, increase in colonic paracellular permeability, and colonocyte MLC phosphorylation. This antinociceptive effect occurs via inhibition of contraction of colonic epithelial cell cytoskeleton and the subsequent tight junction opening, and may also involve direct or indirect effects of NO produced by this probiotic.
应激诱导的结肠细胞旁通透性增加是由上皮细胞细胞骨架收缩引起的，并且是应激诱导的对结肠扩张（CRD）超敏反应的原因。益生菌发酵乳杆菌在体内结肠腔中自发释放一氧化氮（NO）并发挥抗炎作用。本研究旨在：（i）评估发酵乳杆菌对应激诱导的对CRD超敏反应和结肠细胞旁通透性增加的影响；（ii）确定这些作用是否由NO介导以及是否与结肠细胞肌球蛋白轻链磷酸化（p-MLC）的变化有关。
雌性Wistar大鼠在施加部分束缚应激（PRS）或假PRS之前的15天内，每天口服10(11) CFU的发酵乳杆菌或生理盐水。在PRS或假PRS后评估对CRD的内脏敏感性和结肠细胞旁通透性。血红蛋白用作NO清除剂。在PRS或假PRS后，对发酵乳杆菌处理的大鼠和对照大鼠的结肠黏膜进行MLC激酶、MLC和p-MLC的蛋白质印迹分析。
PRS显著增加了30-60 mmHg的CRD压力下的峰电位爆发次数以及结肠细胞旁通透性。发酵乳杆菌处理可预防这两种作用，而血红蛋白可逆转发酵乳杆菌的保护作用。PRS后15至45分钟，p-MLC表达显著增加，而发酵乳杆菌处理可预防这种增加。
发酵乳杆菌处理可预防应激诱导的超敏反应、结肠细胞旁通透性增加和结肠细胞MLC磷酸化。这种抗伤害感受作用是通过抑制结肠上皮细胞细胞骨架收缩和随后的紧密连接开放而发生的，并且可能还涉及这种益生菌产生的NO的直接或间接作用。
