Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods...Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.展开更多
Objective To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury(ALI) in mice. Methods Lipopolysaccharide(LPS, 10 mg/kg) injection or cecal ligation an...Objective To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury(ALI) in mice. Methods Lipopolysaccharide(LPS, 10 mg/kg) injection or cecal ligation and puncture(CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups(n=10 in each group): group A(intraperitoneal LPS injection), group B(intravenous LPS injection via tail vein), group C(CLP with 25% of the cecum ligated), group D(CLP with 75% of the cecum ligated), and the control group(6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin(IL)-6 in serum, bronchoalveolar lavage fluid(BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves(ROC) and computing area under curve(AUC). Results In both group B and group D, most of the "main features" of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI(group A+group C), lipocalin-2 protein expression in septic mice with ALI(group B+group D) was significantly up-regulated in BALF(P<0.01) and in serum(P<0.01), and mRNA expression boosted in lung tissues(all P<0.05). Lipocalin-2 tests performed better than IL-6 tests in recognizing sepsis-induced ALI cases, evidenced by the larger AUC of the former(BALF tests, 0.8800 versus 0.6625; serum tests, 0.8500 versus 0.7000). Using a dual cutoff system to diagnose sepsis-induced ALI, BALF lipocalin-2 test exhibited the highest positive likelihood ratio(13.000) and the lowest negative likelihood ratio(0.077) among the tests of lipocalin-2 and IL-6 in blood and BALF. A statistically significant correlation was found between lipocalin-2 concentration in BALF and that in serum(Spearman r=0.8803,P<0.0001). Conclusions Lipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.展开更多
基金supported by the Anhui Provincial Department of Education Outstanding Young Teachers Cultivation Key Project(No.YQZD2023046)the Anhui University of Traditional Chinese Medicine School Talent Support Program Project(Nos.DT2400000222 and DT2100000545)。
文摘Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.
基金Supported in part by Jie-shou Li Academician Gut Barrier Research Fund(2012001)
文摘Objective To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury(ALI) in mice. Methods Lipopolysaccharide(LPS, 10 mg/kg) injection or cecal ligation and puncture(CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups(n=10 in each group): group A(intraperitoneal LPS injection), group B(intravenous LPS injection via tail vein), group C(CLP with 25% of the cecum ligated), group D(CLP with 75% of the cecum ligated), and the control group(6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin(IL)-6 in serum, bronchoalveolar lavage fluid(BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves(ROC) and computing area under curve(AUC). Results In both group B and group D, most of the "main features" of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI(group A+group C), lipocalin-2 protein expression in septic mice with ALI(group B+group D) was significantly up-regulated in BALF(P<0.01) and in serum(P<0.01), and mRNA expression boosted in lung tissues(all P<0.05). Lipocalin-2 tests performed better than IL-6 tests in recognizing sepsis-induced ALI cases, evidenced by the larger AUC of the former(BALF tests, 0.8800 versus 0.6625; serum tests, 0.8500 versus 0.7000). Using a dual cutoff system to diagnose sepsis-induced ALI, BALF lipocalin-2 test exhibited the highest positive likelihood ratio(13.000) and the lowest negative likelihood ratio(0.077) among the tests of lipocalin-2 and IL-6 in blood and BALF. A statistically significant correlation was found between lipocalin-2 concentration in BALF and that in serum(Spearman r=0.8803,P<0.0001). Conclusions Lipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.
