1.Role of Toll-like receptor 4 in intestinal ischemia-reperfusion and the interventional role of ω-3 polyunsaturated fatty acids
Chinese Journal of Clinical Nutrition 2010;18(5):317-320
Toll-like receptors is a super-family of pathogen recognition-receptors discovered in recent years.During the process of ischemia-reperfusion, the Toll-like receptor 4 (TLR4) combines with lipopolysaccharide and many endogenous ligands such as high mobility group protein B1, heparan sulfate, and fibrinogen. Through the myeloid differentiation protein 88 -dependent and -independent signaling pathways, the products induce the release of inflammatory cytokine-mediated inflammatory response, leading to injuries. ω-3 polyunsaturated fatty acids, by inhibiting the signal pathway activation and target gene expression of TLR4, can influence the function of many immune cells and regulate the body's inflammatory response and immune function. This article reviews the function of TLR4 during ischemia-reperfusion injury and the possible interventional role of ω-3 polyunsaturated fatty acids.
2.The effect of murine intestine ischemia-reperfusion on endogenous ligand of TLR4 expression in distant organs
Kaiguo ZHOU ; Guizhen HE ; Xuefeng CHEN
Chinese Journal of General Surgery 2010;25(9):755-758
Objective To investigate the expression of high mobility group box 1 (HMGBI) of TLR4 endogenous ligand and distant organ tissue injury after intestine ischemia/reperfusion and drainage of lymph fluid in rats. Methods Twenty-four Sprague-Dawley (SD) male rats (SPF grade) were evenly divided into 3 groups:Sham surgery group,intestine ischemia-reperfusion (I/R) group,and intestine ischemia-reperfusion with drainage of intestine lymph fluid (IR + drainage) group.The injury of distant organs such as lungs,liver,kidney was evaluated;The expression of high mobility group box 1 (HMGBI) of TLR4 endogenous ligand in intestine,lung and liver after the ischemia-reperfusion injury was measured by immunohistochemistry.Result HE stained sections,as well as HMGB1 immunohistochemistry results showed that the injury of ischemia/reperfusion (I/R) group and ischemia/reperfusion (I/R) + drainage group were more severe than that in the sham group.A large number of cells stained in I/R group,indicating that HMGB1 expression increased.The injury in I/R + drainage group was significantly less severe than I/R group.Western blot tests showed that the expression of HMGB1 in jejunum,ileum,liver,lung increased significantly in I/R group after L/R injury.Gray-scale values of HMGB1/β-actin were 0.3145 ± 0.0549、 1.7352 ± 0.3280、1.4443 ± 0.0926、3.1382 ± 0.4202.Lymph drainage significantly alleviated the damage,the expression of HMGB1 were significantly lower (P <0.05).Gray-scale values of HMGB1/β-actin were 0.1745 ± 0.0327、 1.1083 ± 0.2098、 1.1862 ± 0.1221、2.1095 ± 0.1993. Conclusion Increased expression of HMGB1 of TLR4 endogenous ligand is associated with intestinal and distant tissue injury during intestinal ischemia-reperfusion injury.Drainage of lymph fluid can block the gutlymph pathway and thus reduce the source of HMGB1 from the intestinal as well as the injury of distant tissue.
3.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.
4.The effects of different pre-hospital intervention of treatment modes on the prognosis of patients with severe multiple trauma
Kaiguo ZHOU ; Jianzhong LI ; Huilin JIA ; Bingchen MA ; Qiumei CAO
Chinese Journal of Emergency Medicine 2016;25(3):362-366
Objective To investigate the effects of different treatment modes on the prognosis of patients with severe trauma.Methods The general data of 396 patients with severe trauma [injurey severity scores (ISS) ≥25] in our hospital emergency for treatment from January 1,2008 to January 1,2012 was collected.The trauma patients were divided into study group and control group.In the study group,the trauma patients were cared by emergency physician of our hospital for pre-hospital treatment during transportation by ambulance since January 1,2010.In the control group,the trauma patients were served with traditional pre-hospital emergency care by the 120 and 999 before January 1,2010.The injury severity score,medical care and outcomes were recorded in trauma database and the efficiency and quality of medical care were compared between two groups.Results The emergency treatment time,length of hospital stays,ICU admission rate,prehospital mortality rate,long-term (6 months) disability rate,and complication rate in the study group were lower than those in the control group,presenting (78.23 ± 21.57) min vs.(96.45 ± 35.14) min,(23.55±12.46) dvs.(28.67±20.72) d,8.1% (18/222)vs.65.5% (114/174),13.3% (34/256) vs.21.6% (48/222),4.1% (9/222)vs.9.2% (16/174),8.1% (18/222)vs.18.4% (32/174),in which the differences were statistically significant (P < 0.05).Hospital mortality in the study group was also lower than that in the control group,showing 8.1% (18/222) vs.12.6% (22/174),but there was no statistically significant difference (P < 0.05).There was no significant difference in time from occurrence of injury to receiving treatment between the two groups.Conclusion Emergency physicians-cared mode had advantages to improve treatment success rates and reduce mortality in patients with multiple trauma compared with the current conventional emergency mode.It is a good alternative emergency mode.
5.Effects of ω-3 polyunsaturated fatty acids intervention on Toll-like receptor 4 and high mobility group box 1 with intestinal ischemia/reperfusion injury
Guizhen HE ; Kaiguo ZHOU ; Xuefeng CHEN ; Yukang WANG ; Fie WANG
Chinese Journal of Clinical Nutrition 2013;(3):147-156
Objective To investigate the expressions of Toll-like receptor 4 (TLR4) and high mobility group box 1 (HMGB1) expression on distant tissue during the intestinal ischemia/reperfusion and the effects of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) intervention in rats.Methods Forty-eight Sprague-Dawley male rats,weighing (281.50 ± 22.68) g,were randomly divided into three groups (n =16) after gastrostomy:normal diet (N) group,enteral nutrition (EN) group and EN plus ω-3 PUFAs (PUFA) group.Each group was further divided into lymph drainage (I/R + D) and non-drainage (I/R) sub-groups (n =8 each) according to whether treated with intestinal lymph drainage.All the rats were subjected to 60 min ischemia by clamping the superior mesenteric artery,followed by 120 min reperfusion,while the rats in the I/R + D subgroups were treated with intestinal lymph drainage for 180 min at the same time.Results The interleukin-6 level in lymph in N (I/R + D) group was significantly higher than in the EN (I/R + D) and PUFA (I/R + D) groups (PUFA vs EN vs N:(154.57 ±69.30) ng/L vs (97.58 ±40.34) ng/L vs (85.35 ±23.93) ng/L,P =0.021).Besides,the serum level of HMGB1 in PUFA (I/R + D) group was significantly lower compared to the other 5 groups [PUFA (I/R) vs EN (I/R) vs N (I/R) vs PUFA (I/R + D) vs EN (I/R + D) vs N (I/R + D):(2.95 ± 1.17) μg/L vs (3.86 ±0.99) μg/L vs (4.45 ± 1.73) μg/L vs (1.71 ±1.41) μg/Lvs (2.11±0.56) μg/Lvs (3.13 ±0.79) μg/L,P=0.000],and it also decreased in the PUFA (I/R) and EN (I/R) groups than the N (I/R) group (respectively,P < 0.05).Furthermore,the serum endotoxin level in PUFA (I/R) group was significantly lower compared to the N (I/R) and EN (I/ R) groups[PUFA(I/R) vsPUFA (I/R+D) vsEN (I/R) vs N (I/R):(0.020±0.004) EU/mlvs (0.028 ±0.006) EU/ml vs (0.028 ±0.005) EU/ml vs (0.018 ±0.006) EU/ml,P=0.014].Together the serum tumor necrosis factor-α level in both PUFA (I/R) and PUFA (I/R + D) groups were significantly lower than theEN (I/R),N (I/R) and N (I/R+D) groups [PUFA (I/R+D) vs PUFA (I/R) vs EN (I/R) vsN (I/R) vs N (I/R+D):(12.03 ±6.57) ng/L vs (14.32 ±6.11) ng/Lvs (23.27 ±15.60)ng/L vs (27.42 ± 10.37) ng/L vs (26.87 ± 5.30) ng/L,P =0.013].The jejunum and ileum mucosa in all the I/R groups showed swelling and atrophy and appeared fragile,while the PUFA groups showed less yellow staining and injury than the other two groups (P < 0.05,respectively).In addition,the expressions of TLR4 mRNA in jejunum,ileum,and liver in all the drainage groups were respectively lower than the corresponding non-drainage groups [jejunum:PUFA (I/R) vs EN (I/R) vs N (I/R) vs PUFA (I/R+D) vs EN (I/R+D) vsN (I/R+D):2.32±0.62vs3.08±1.29vs3.50±2.44vs 1.62±0.79vs 1.67±1.11 vs 1.94±0.81,P=0.025; ileum:PUFA (1/R) vsEN (1/R) vsN (1/R) vs PUFA (1/R+D) vsEN (1/R+D) vs N (1/R+D):2.67±1.08 vs 5.22 ± 3.96 vs 6.95 ±4.92 vs 1.70±0.68 vs 1.80±0.29 vs3.68±1.47,P=0.012; liver:PUFA (1/R)vsEN (1/R)vsN (1/R)vs PUFA (1/R+D)vsEN (1/R+D)vsN (1/R+D):5.67 ±1.94 vs 7.50 ±3.89 vs 7.18 ±4.55 vs 1.70 ±0.86 vs 3.90 ± 1.95 vs 4.12 ±2.11,P =0.001],which was consistent with the reduction of HMGB1 and the decrease of nuclear factor-κB activity in intestine,liver,and lung (P =0.000).Conclusions Lymph drainage and ω-3 PUFAs intervention can reduce the production of HMGB1 and inflammation factors,inhibit the expression of HMGB1 and TLR4 mRNA,and thus alleviate distant tissue injury caused by intestinal L/R.
6.Effects of ropivacaine infiltration combined with dezocine intravenous on stress response during recovery from general anesthesia in patients undergoing esophageal cancer surgery
Yonglai ZHANG ; Rui SHA ; Jingyu LIU ; Kaiguo WANG ; Hao LI ; Bo YAN ; Naibao ZHOU
The Journal of Clinical Anesthesiology 2016;(2):139-143
Objective To investigate the effects of ropivacaine infiltration combined with dezo-cine intravenous on stress response during recovery from general anesthesia in patients undergoing e-sophageal cancer surgery.Methods One hundred and forty-four patients of esophageal cancer under-going elective surgery were randomly divided into dezocine group (group D,n = 48 ),ropivacaine group (group R,n =47)and ropivacaine combined with dezocine group (group RD,n =49 ).Before slicing 10 min,patients in group D were taken 20 ml saline infiltration anesthesia (1∶200 000 epi-nephrine),while in group R and group RD were taken 20 ml 0.5% ropivacaine infiltration anesthesia. Patients in the group R were injected intravenously 2 ml saline,while in group D and group RD were injected intravenously 10 mg dezocine 30 min before the end of surgery.Peri-operative bleeding,oper-ation time,recovery time of anesthesia,extubation time and the dosage of propofol and sufentanil of three groups were recorded respectively.At the time points of before induction of anesthesia (T0 ), the end of the surgery (T1 ),removal trachea immediate (T2 ),10 min (T3 )and 30 min (T4 ),the blood pressures and heart rates were recorded,and the serum levels of malondialdehyde (MDA),epi-nephrine (E)and norepinephrine (NE)were detected.Results Recovery time of anesthesia and extu-bation time in group R and group RD were shorter than that in group D significantly (P <0.05).The dosage of propofol and sufentanil in group R and group RD were less than that in group D significantly (P <0.05).Compared with T0 ,SBP in three groups were elevated significantly at T1-T4 (P <0.05), DBP and HR in group D and group R increased significantly at T3 (P <0.05).DBP and HR in group RD at T3 were lower than that in group D and group R significantly (P <0.05).Compared with T0 , the levels of blood sugar,Cor,MDA,E and NE in three groups were elevated significantly at T1-T4 (P <0.05).The levels of blood sugar,Cor,MDA,E and NE in group RD at T1-T4 were lower than that in group D and group R significantly(P < 0.05 ).The incidences of agitation and elevation of blood pressure in group RD were lower than that in group D and group R significantly (P <0.05 ). Conclusion Ropivacaine infiltration combined with dezocine intravenous applied in the esophageal cancer surgery could effectively reduce the stress response during recovery from anesthesia,and de-crease the incidence of agitation.