Effects of ω-3 polyunsaturated fatty acids intervention on Toll-like receptor 4 and high mobility group box 1 with intestinal ischemia/reperfusion injury / 中华临床营养杂志

ABSTRACT

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 gastrostomynormal 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 [jejunumPUFA (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; ileumPUFA (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; liverPUFA (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.