1.Effect of Toll like receptor 4 and its endogenous ligands in ischemia-reperfusion injury
Xuefeng CHEN ; Guizhen HE ; Liangguang DONG
Basic & Clinical Medicine 2006;0(12):-
TLR4 mediates I/R injury involving endogenous ligands.Interaction of TLR4 with endogenous ligands provides a critical link between tissue damage and activation of the innate immune response.In the early phase of liver,kidney,heart,or lung I/R injury,endogenous ligands are secreted from several kinds of cells,they are recognized by TLR4.Interaction of TLR4 with endogenous ligands,such as HMGB1,seems to be the most important trigger of inflammation and initiates signaling cascades leading to inflammatory and immune responses.Blocking the interaction of TLR4 with endogenous ligands may be useful in clinical management of inflammation and cellular necrosis caused by ischemic insults.
2.Effect of ω-3 polyunsaturated fatty acids on intestinal ischemiareperfusion injury and lymphatic duct ligation
Guizhen HE ; Liangguang DONG ; Kaiguo ZHOU ; Xuefeng CHEN
Chinese Journal of Clinical Nutrition 2010;18(2):95-100
Objective To investigate the effect of intestinal lymphatic duct ligation and ω-3 polyun saturated fatty acids on intestinal and distant organ in intestinal ischemia-reperfusion injury. Methods Totally 40Sprague-Dawley (SD) male rats (SPF grade)after gastrostomy were equally randomized into sham group (Sham), enteral nutrition (EN) group, enteral nutrition and lymphatic duct ligation (EN + L) group, ω-3 polyunsaturated fatty acids (ω-3PUFA) group, and ω-3PUFA and lymphatic duct ligation (ω-3PUFA + L) group. After 7 days of nutritional intervention, rats were subjected to 60 minutes of intestinal ischemia, ischemia plus mesenteric lymph duct ligation, or sham procedures. After 3 days of continuous nutrition intervention using the original nutrient, lymph nodes, lung, intestine, liver, and blood specimens were harvested. Intestinal permeability and morphology, results of bacterial cultures, and serum cytokines were observed or detected. Result After 3 days of intestinal ischemia-reperfusion (I/R), the body weights of rats in EN group significantly decreased when com pared with the pre-I/R levels (P < 0.05), while the body weights of rats in EN + L group were significantly lower than those in ω-PUFA group and ω-PUFA + L group (P < 0. 05). After one day of intestinal ischemia-reperfusion (I/R), the L/M significantly increased in each group (P <0.05 or P <0. 01). After 3 days of intestinal ischemiareperfusion (I/R) , the L/M were significantly lower than the level one day after ischemia- reperfusion in EN + L group, ω-PUFA group, and ω-PUFA + L group (P < 0.05). The L/M in EN group and EN + L group were significantly higher than that in ω-PUFA + L group (P < 0. 05). The mucosa thickness and villus height of jejunum in ω-PUFA group and ω-PUFA + L group were significantly higher than those in Sham group, EN group, and EN + L group (P < 0. 01 or P < 0. 05). The mucosa thickness and villus height of ileum in ω-PUFA group and ω-PUFA +L group were also significantly higher than those in EN group (P < 0.05). In ω-PUFA + L group, the serum endotoxin level and tumor necrosis factor-α level were significantly lower than those in EN group (P < 0.05), interleukin (IL) -6 level was significantly lower than that in the ω-PUFA group (P < 0.05), and IL-1 β level was significantly lower than those in other groups (P < 0. 05). In EN group, the lung cell apoptosis index was significantly higher than those in other groups (P < 0.05)and the levels of inducible nitric oxide synthase (iNOS)and myeloperoxidase (MPO) were significantly higher than those in ω-PUFA + L group (P < 0. 05). The level of iNOS was also significantly higher in EN + L group than that in ω-PUFA + L group (P < 0.05). Conclusions Sixty minutes of intestinal ischemia can cause intestinal injury, intestinal barrier dysfunction, and increased permeability of intestine. After 72 h of reperfusion, the intestinal injury can be partially recovered and the permeability can be lower than the post-ischemia level; however, bacterial endotoxin translocation and lung apoptotic cells still exist. Intestinal lymphatic ligation can alleviate the lung damage, promote repair of intestinal mucosa, reduce endotoxin translocation, and attenuate the systemic inflammatory response. EN added with ω-3PUFA is remarkably superior to conventional EN.
3.Change of high mobility group box 1 and effect of drainage of intestine lymph fluid on rat gut barrier during intestine ischemia-reperfusion
Xuefeng CHEN ; Guizhen HE ; Liangguang DONG ; Xiaoyu CUI ; Hong SHU ; Xiurong WANG ; Dongmei FAN
Chinese Journal of Clinical Nutrition 2009;17(2):91-94,Ⅰ
Objective To investigate the change of high mobility group box 1 ( HMGBI ) after intestine ischemia reperfusion (I/R) in rats, compare the effect of drainage of intestine lymph fluid on gut barrier, and ex- plore the possible mechanism of iachemia-reporfusion injury. Methods Thirty-two Sprague-Dawley (SD) rats (SPF grade) were randomly divided into4 groups with 8 rats in each group: blank group, sham group, intestine is-chemia-reperfusion (I/R) group, and intestine ischemia-reperfusion with drainage of intestine lymph fluid (I/R +drainage) group. Indicators of gut barrier function damage, translocation of endotoxin, and change of HMGB1 and cytokines were detected after intestine ischemia-reperfusion injury. Results The gut barrier function damage and levels of endotoxin, HMGBI, tumour necrosis factor-alpha ( TNF-α), interleukin-6 ( IL-6 ), interleukin-1 beta (IL-1β), and soluble intercellular adhesion molecule-1 (sICAM-1) were significantly lower in blank group and sham group than in I/R group and I/R + drainage group ( P < 0. 05 ). Compared with the intestine I/R + drainage group, the levels of endotoxin and cytokines were significantly higher in the intestine I/R group. The level of HMGB1 was slightly higher than that in the intestine I/R + drainage group, but such difference was not statistically significant ( P > 0. 05 ). lmmunohistochemical staining also revealed that the expression of HMGB1 was significant- ly higher in I/R group than in I/R + drainage group. Conclusions Intestine iachemia-reperfusion injury can lead to the injury of intestine mucosal barrier and increase HMGB1 level HMGB1 may deteriorate gut barrier function and increase the leveh of systemic cytokines. Drainage of lymph fluid can block the gut-lymph pathway and thus decrease the levels of endotoxin and cytokines in systemic circulation and attenuate intestine ischemia-reperfusion injury.