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Objective To investigate the reduce of experimental autoirnmune encephalomyelitis(EAE) susceptivity after lipopolysaccharide (LPS) exposure in neonatal rats and its relation with inhibition of macrophage immune function.Methods Litter male neonatal rats were divided into blank control group (n=1 1),phosphate buffer (PBS) group (n=12) and LPS group (n=12);rats in the LPS group were performed intraperitoneal injection of 50 μL LPS on postpartum day 3 and 5.Rats in the PBS group and LPS group were established EAE models by immune induce of spinal cord homogenate of guinea pig with complete Freund's adjuvant at 12 weeks old,while rats in the blank control group were given immune induce of complete Freund's adjuvant.Since the day of induce,the behavioral scale scores of all the rats were assessed.On the 20th d,all rats were sacrificed and paraffin sections were cut and stained with HE to detect inflammatory cell infiltration.The number of infiltrating macrophages and the expressions of CD86,CD80,MHC-Ⅱ were determined by flow cytometry.The transcriptional levels of C-C chemokine receptor type 2 (CCR2),interleukin (IL)-1β and tumor necrosis factor (TNF)-α in macrophages were determined by real-time fluorogenic quantitative PCR.Results As compared with the PBS group,LPS group had significantly lower EAE incidence (11/12 vs.5/12) and higher EAE latency ([10.50±0.71] d vs.[12.17± 1.17] d),and statistically decreased cumulative clinic scores and peak clinic scores (20.00±9.13 vs.5.58±7.12;2.58±1.08 vs.1.03±0.83,P＜0.05).The inflammation in the spinal cord of the PBS group was severer than that in the LPS group (2.83±0.75 vs.1.17±1.17,P＜0.05).The number of infiltrating macrophages of the PBS group was significantly larger than that in the LPS group ([202.70 ±81.89] × 103 cells vs.[92.58 ±42.65] × 103 cells,P＜0.05).The expressions of CD80 and MHC-Ⅱ,and mRNA levels of CCR2,IL-1β and TNF-α in the PBS group were significantly higher than those in the LPS group (P＜0.05).Conclusion Neonatal LPS exposure reduces the severity of EAE,which may relate to impaired macrophage immune function.
RESUMEN
AIM: To investigate the effects of non-invasive ischemic preconditioning on nitric oxide (NO)/endothelin-1 (ET-1) imbalance and gas exchange impairment following limb ischemia reperfusion in patients undergoing unilateral lower extremity surgery with tourniquet. METHODS: Twenty-seven patients aged 25-65 years, whose tourniquets duration varied from 1 h to 1.5 h and matched American Society of Anesthesiologists Physical Status Ⅰ-Ⅱ, were randomized into two groups: a control group (n=14) and a ischemic preconditioning group (IPC group, n=13) in which patients received three cycles of 5 min of ischemia/5 min of reperfusion before tourniquet inflation. Radial arterial blood gas, plasma malondialdehyde (MDA) and NO, serum ET-1 and interleukin-6 (IL-6) were measured just before tourniquet inflation(T_0), 1 h after inflation(T_1), and 0.5 h(T_2), 2 h(T_3), 6 h(T_4), 24 h(T_5) after tourniquet deflation. Meanwhile NO/ET-1 ratio, alveolar-arterial oxygen gradient (P_(A-a)DO_2) and intrapulmonary shunt (Qs/Qt) were calculated. RESULTS: In control group, arterial partial pressure of oxygen (PaO_2) were decreased, while P_(A-a)DO_2 and Qs/Qt were increased significantly at T_4 compared to the baselines at T_0 (P<0.01). Plasma NO levels and NO/ET-1 ratios decreased gradually after tourniquets deflation and statistical significances were observed at T_3 (P<0.01) with a valley at T_4 (P<0.01) and recovered to baselines at T_5. Serum ET-1, IL-6 and plasma MDA began to increase remarkably after T_3 (P<0.05 or P<0.01), peaked at T_4 and dropped slightly at T_5. The changes above-mentioned could be well attenuated by the application of IPC (P<0.05 or P<0.01) except PaO_2 (P>0.05). CONCLUSION: Clinical application of unilateral tourniquet within safe time limit (1.5 h) may lead to limb ischemia reperfusion and further pulmonary gas exchange impairment, which could be partially attenuated by the application of IPC via alleviating NO/ET-1 imbalance.