浙江中西医结合杂志

潘杭丽,伍慧丽.肝素调控JAK-STAT信号通路对川崎病小鼠血红蛋白的影响[J].浙江中西医结合杂志,2025,35(1):

肝素调控JAK-STAT信号通路对川崎病小鼠血红蛋白的影响

Effect of heparin regulating JAK-STAT signal pathway on hemoglobin in mice with Kawasaki disease

投稿时间：2024-03-28 修订日期：2024-10-21

DOI：

英文关键词:mice Kawasaki disease signal pathway Hepcidin hemoglobin

基金项目:杭州市医药卫生科技项目；浙江省中医药科技计划项目

作者	单位	E-mail
潘杭丽^*	浙江中医药大学附属杭州市中医院	465916769@qq.com
伍慧丽	浙江中医药大学附属杭州市中医院

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中文摘要:

目的：探讨肝素通过Janus激酶/信号传导和转录激活蛋白（JAK/STAT）JaK-STAT信号通路对川崎病(KD)模型小鼠血红蛋白的调节作用。方法：将 C57小鼠随机分为对照组、模型组、肝素治疗组，每组15只。对照组腹腔注射磷酸盐缓冲液（PBS）[4 mg/(只·天)d，连续5 天]d后，后每天腹腔注射安慰剂[（0.9%氯化钠溶液）（NS），连续7 天]d；模型组腹腔注射白色念珠菌细胞壁水溶性成份（CAWS）[4 mg/(只·天)d，连续5 天]d后，后每天腹腔注射0.9%氯化钠溶液安慰剂(NS，连续7 天)d；肝素治疗组腹腔注射(CAWS)[ 4 mg/(只·天)d，连续5 5天]d后，后每天腹腔注射肝素 (0.1 U/kg，连续7 天)d。监测小鼠体重质量，全血细胞分析仪检测血红蛋白水平（Hb），酶联免疫吸附试验测定（ELSIA）测定测小鼠血清中白细胞介素-6（IL-6），和铁调素（Hepcidin）含量水平，蛋白质印记法（Western blot）检测各组小鼠肝脏组织JAK-STAT中Janus激酶/信号传导和转录激活蛋白（Jak/STAT）信号通路相关蛋白的表达，实时荧光定量PCR技术（RT-qPCR）检测JAK-STATJak/STAT信号通路相关mRNA的表达。结果：随着实验天数的增加，与对照组比较，模型组体重质量下降 [（21.29±0.39g）g比(29.40±0.66g)g，,P＜0.05] ,，Hb含量血红蛋白水平下降[(102.61±8.03g/L)g/L比(150.33±120.10g/L)g/L，,P＜0.05]，血清IL-6[（68.05±0.39）pg/mL比（26.71±1.30）pg/mL，P＜0.05]、铁调素[（332.93±15.99）ng/mL比（99.58±4.61）ng/mL，P＜0.05]含量水平升高[IL-6：（68.05±0.39pg/ml）比(26.71±1.30pg/ml),P＜0.05;铁调素:(332.93±15.99ng/ml）比(99.58±4.61ng/ml),P＜0.05]，肝脏组织中p-JAK1[(1.30±0.09）比（0.16±0.01），P＜0.05]、JAK1[（1.27±0.07）比（0.14±0.02），P＜0.05]、p-JAK2[（1.14±0.08）比（0.14±0.03），P＜0.05]、JAK2[（1.27±0.07）比（0.27±0.03），P＜0.05]、p-STAT3[（1.09±0.07）比（0.11±0.02），P＜0.05]、STAT3[（1.11±0.08）比（0.28±0.03），P＜0.05]蛋白表达上升[pJAK1:(1.3±0.09）比(0.16±0.01),P＜0.05;JAK1: (1.27±0.07）比(0.14±0.02),P＜0.05；pJAK2: (1.14±0.08）比(0.14±0.03),P＜0.05；JAK2：(1.27±0.07）比(0.27±0.03),P＜0.05；pSTAT3：(1.09±0.07）比(0.11±0.02),P＜0.05；STAT3：(1.11±0.08）比(0.28±0.03),P＜0.05]。RT-qPCR检测肝脏组织，中JAK1[（3.05±0.23）比（0.98±0.08），P＜0.05]、JAK2[（3.82±0.50）比（0.96±0.05），P＜0.05]，、STAT3[（4.58±0.34）比（0.95±0.08），P＜0.05] mRNA的表达上升[JAK1: (3.05±0.23）比(0.98±0.08),P＜0.05；JAK2：(3.82±0.50）比(0.96±0.05),P＜0.05；STAT3：(4.58±0.34）比(0.95±0.08),P＜0.05]。与模型组比较,，肝素治疗组体重质量上升[(（27.11±0.58）g)g比(（21.29±0.39）g)g，,P＜0.05] ,，Hb含量血红蛋白水平上升[(（150.65±9.53）g/L)比(（102.61±8.03）g/L),，P＜0.05] ，血清IL-6[（36.73±3.40）pg/mL比（68.05±0.39）pg/mL，P＜0.05]、铁调素含量下降[IL-6:(36.73±3.40pg/ml）比68.05±0.39pg/ml),P＜0.05;铁调素:[(（167.49±10.72）ng/ml）L比(（332.93±15.99）ng/ml)L,，P＜0.05]水平下降，肝脏组织中p-JAK1[（0.31±0.04）比（1.30±0.09），P＜0.05]、JAK1[（0.26±0.02）比（1.27±0.07），P＜0.05]、p-JAK2[（0.45±0.05）比（1.14±0.08），P＜0.05]、JAK2[（0.47±0.05）比（1.27±0.07），P＜0.05]、p-STAT3[（0.46±0.04)比（1.09±0.07），P＜0.05]、STAT3[（0.64±0.04）比（1.11±0.08），P＜0.05]蛋白表达下降[pJAK1:(0.31±0.04）比(1.3±0.09),P＜0.05;JAK1: (0.26±0.02)比(1.27±0.07),P＜0.05;pJAK2: (0.45±0.05）比(1.14±0.08),P＜0.05;JAK2：(0.47±0.05）比(1.27±0.07),P＜0.05；pSTAT3:(0.46±0.04)比(1.09±0.07),P＜0.05；STAT3:(0.64±0.04)比(1.11±0.08)]。RT-qPCR检测肝脏组织中，JAK1[（1.38±0.10）比（3.05±0.23），P＜0.05]、JAK2[（1.42±0.09）比（3.82±0.50），P＜0.05]，、STAT3[（1.95±0.12）比(4.58±0.34），P＜0.05]mRNA的表达下降[JAK1: (1.38±0.10）比(3.05±0.23),P＜0.05；JAK2：(1.42±0.09）比(3.82±0.50),P＜0.05；STAT3：(1.95±0.12）比(4.58±0.34),P＜0.05]。结论：肝素可有效提高KD川崎病模型小鼠模型血红蛋白水平。，其作用机制可能通过调控JakAK-STAT信号通路，降低铁调素水平相关。

英文摘要:

Objective To investigate the regulatory effect of heparin on hemoglobin in Kawasaki disease (KD) mice through Janus kinase/Signal transduction and Transcriptional Activator protein (JAK/STAT) signaling pathway Explore the regulation of heparin through the Jak-STAT signaling pathway to Kawasaki Disease (KD) mice hemoglobin. Methods C57 mice were randomly divided into control group, model group and heparin group, with 15 mice in each group. The control group was given intraperitoneal injection of PBS solution （[4 mg/(piece · day) for 5 consecutive days]）, After that, placebo was given every day (NS for 7 consecutive days). model group was given intraperitoneal injection of water soluble components of Candida albicans cell wall (CAWS) ([4 mg/(piece · day) for 5 consecutive days]), and then daily placebo (NS, 7 consecutive days). The heparin group was given intraperitoneal injection of heparin (0.1U/kg for 7 consecutive days) every day after the injection of ([4 mg/(piece · day) for 5 consecutive days] ). Monitor the weight of mice. Detection of Hb and HCT by whole blood cell analyzer. Determination of IL-6 and Hepcidin in serum by ELSIA. Western blot method was used to detect the expression of Jak/STAT signal pathway related protein in liver tissues of each group. Detection of Jak/STAT signal pathway mRNA expression in liver tissue by RT-qPCR. Results With the increase of the number of experiments, compared with the control group, the weight of the model group was decreased [weight:（21.29±0.39g）gvs(29.40±0.66g)g,P＜0.05] ，HB content decreased[Hb:(102.61±8.03g/L)g/Lvs(150.33±120.10g/L)g/L,P＜0.05] ，increased secretion levels of IL-6 and hepcidin [IL-6：（68.05±0.39pg/ml）pg/mlvs(26.71±1.30pg/ml)pg/ml,P＜0.05;hepcidin:(332.93±15.99ng/ml）ng/mlvs(99.58±4.61ng/ml)ng/ml,P＜0.05], PJAK1, JAK1, PJAK2, JAK2, PSTAT3, STAT3 protein expression in liver tissue increase [pJAK1:(1.30±0.09）vs(0.16±0.01),P＜0.05;JAK1: (1.27±0.07）vs(0.14±0.02),P＜0.05；pJAK2: (1.14±0.08）vs(0.14±0.03),P＜0.05；JAK2：(1.27±0.07）vs(0.27±0.03),P＜0.05；pSTAT3：(1.09±0.07）vs(0.11±0.02),P＜0.05；STAT3：(1.11±0.08）vs(0.28±0.03),P＜0.05]，RT-qPCR test the expression of JAK1, JAK2, STAT3 mRNA in liver tissue increased [JAK1: (3.05±0.23）vs(0.98±0.08),P＜0.05；JAK2：(3.82±0.50）vs(0.96±0.05),P＜0.05；STAT3：(4.58±0.34）vs(0.95±0.08),P＜0.05]。Compared with the model group, the heparin group has increased weight[weight:（27.11±0.58g）gvs(21.29±0.39g)g,P＜0.05] , the Hb rised [Hb:(150.65±9.53g/L)g/Lvs(102.61±8.03g/L)g/L,P＜0.05],decreased secretion levels of IL-6 and hepcidin [IL-6：（36.73±3.40）pg/ml vs( 68.05±0.39)pg/ml),P＜0.05; hepcidin :(167.49±10.72ng/ml）ng/mlvs(332.93±15.99ng/ml)n,P＜0.05]，PJAK1, JAK1, PJAK2, JAK2, PSTAT3, STAT3 protein expression in liver tissue declines [pJAK1:(0.31±0.04）vs(1.3±0.09),P＜0.05;JAK1: (0.26±0.02）vs(1.27±0.07),P＜0.05；pJAK2: (0.45±0.05）vs(1.14±0.08),P＜0.05；JAK2：(0.47±0.05）vs(1.27±0.07),P＜0.05；pSTAT3：(0.46±0.04）vs(1.09±0.07),P＜0.05；STAT3：(0.64±0.04）vs(1.11±0.08)]。RT-qPCR detects the expression of JAK1, JAK2, STAT3 mRNA in liver tissue decline [JAK1: (1.38±0.10）vs(3.05±0.23),P＜0.05；JAK2：(1.42±0.09）vs(3.82±0.50),P＜0.05；STAT3：(1.95±0.12）vs(4.58±0.34),P＜0.05]。Conclusion Hepcidin can effectively increase the hemoglobin level of KD mice model. Its mechanism of action may be related to the reduction of Hepcidin level by regulating JAKJak-STAT signal pathway.

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