JAK/STAT信号通路在大鼠重症急性胰腺炎早期作用机制的研究

程峰; 邱兆磊; 郑传明; 夏雅琴; 李磊; 杜召辉; 姜海; 王振杰; 解福臣

doi:10.16766/j.cnki.issn.1674-4152.002807

JAK/STAT信号通路在大鼠重症急性胰腺炎早期作用机制的研究

doi: 10.16766/j.cnki.issn.1674-4152.002807

1.
蚌埠医学院第一附属医院急诊外科, 安徽蚌埠 233004
2.
蚌埠医学院临床医学一系, 安徽蚌埠 233003

基金项目:

安徽省教育厅重点项目 KJ2019A0385

蚌埠医学院自然科学基金项目 BYKY1779

安徽省大学生创新创业训练计划项目 S201910367121

蚌埠医学院自然科学重点项目 BYKY2019095ZD

蚌埠医学院自然科学重点项目 2021byzd160

详细信息

通讯作者:
郑传明，E-mail：609972814@qq.com

中图分类号: R657.51 R-332
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- 被引次数: 0
出版历程
- 收稿日期: 2022-01-22
- 网络出版日期: 2023-04-07

Mechanism of JAK/STAT signaling pathway in the early stage severe acute pancreatitis rats

1.
Department of Emergency Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

摘要

摘要: 目的探讨抑制JAK/STAT信号通路对大鼠重症急性胰腺炎(SAP)早期相关疾病指标的影响，从而推测该信号通路在SAP大鼠中可能的作用机制。方法将54只成年SD大鼠按随机数字表分成对照组、SAP组、AG490组，每组18只，AG490组造模前给予AG490，其他组给予等量生理盐水，以5%牛磺胆酸钠逆行胆胰管内注射法制作SAP模型，造模后6、12、24 h每组分别处死6只大鼠，取心房血测血淀粉酶、血钙、TNF-α、IL-1、IL-6，留取胰腺组织行HE染色病理检查及Western blotting法检测胰腺组织中STAT3蛋白表达水平。结果 AG490组在6、12、24 h淀粉酶值分别为(2 049.17±257.00)U/L、(2 915.00±188.42)U/L、(3 746.50±181.05)U/L，高于对照组、低于SAP组，SAP组高于对照组(均P＜0.05)；AG490组6、12、24 h血钙浓度高于SAP组, 2组均低于对照组(均P＜0.05)；AG490组6、12、24 h TNF-α、IL-6、IL-1均低于SAP组，2组均高于对照组；SAP组胰腺组织STAT3表达量随时间增加，24 h明显高于AG490组，其他时间点差异不明显。SAP组、AG490组胰腺病理切片可见胰腺细胞水肿、炎性细胞浸润，差异不明显。结论 SAP早期阶段可能是通过JAK/STAT信号通路诱导多种炎性因子分泌，促进胰腺炎的进展。
- 重症急性胰腺炎 /
- 酪氨酸蛋白激酶 /
- 信号转导及转录激活因子 /
- 信号通路
Abstract: Objective To investigate the effect of inhibiting JAK/STAT signaling pathway on relevant disease indicators in rats with early stage severe acute pancreatitis (SAP), so as to speculate the possible mechanism of this signaling pathway in SAP rats. Methods Fifty-four adult SD rats were divided into control group, SAP group and AG490 group according to random number table, 18 rats in each group. AG490 group was given AG490 application before modeling, other groups were given equal amount of saline. SAP model was made by retrograde intra-biliary pancreatic duct injection with 5% sodium taurocholate, and the rats were executed at 6 h, 12 h and 24 h after modeling, and atrial blood was taken to measure serum amylase, calcium, TNF-α and calcium. The pancreatic tissues were examined by HE staining. Western blotting was used to detect the expression level of STAT3 protein in pancreatic tissues. Results The amylase values in the AG490 group at 6 h, 12 h and 24 h were (2 049.17±257.00) U/L, (2 915.00±188.42) U/L and (3 746.50±181.05) U/L, respectively, which were higher than those in the control group and lower than those in the SAP group, and SAP group was higher than the control group (all P < 0.05). The blood calcium concentrations at 6 h, 12 h and 24 h in the AG490 group were higher than those in the SAP group, both groups were lower than the control group (all P < 0.05). The TNF-α, IL-6 and IL-1 at 6 h, 12 h and 24 h in the AG490 group were lower than those in the SAP group, and both groups were higher than the control group. STAT3 expression in SAPgrouppancreatic tissue increased with time between groups, and the 24 h point was significantly higher than the AG490 group, with insignificant differences at other points. AG490 group, pancreatic cell edema and inflammatory cell infiltration were seen in pathological sections, no significant difference. Conclusion The early stage of severe acute pancreatitis may induce multiple inflammatory factors through the JAK/STAT signaling pathway and promote the progression of pancreatitis.
- Severe acute pancreatitis /
- Tyrosine protein kinase /
- Signal transduction and transcriptional activator /
- Signaling pathways

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图 1 各组大鼠不同时间点血淀粉酶、血钙浓度变化情况

注：A为淀粉酶变化情况，B为血钙浓度变化情况。

Figure 1. Changes of serum amylase and calcium concentration in each group at different time points

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图 2 各组大鼠胰腺组织STAT3的表达

注：A为空白对照，B为SAP组和AG490组，对照组为空白(从左至右依次为SAP 24 h组、SAP 12 h组、SAP 6 h组、AG490 6 h组、AG490 12 h组、AG490 24 h组)。

Figure 2. The expression of STAT3 in pancreatic tissue of rats in each group

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图 3 各组大鼠胰腺组织病理(HE染色，×200)

注：A为对照组24 h；B为SAP组24 h；C为AG490组24 h。

Figure 3. Pancreatic histopathology of rats in each group (HE staining, ×200)

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表 1 各组大鼠血清淀粉酶、血钙水平比较(x ±s)

Table 1. Comparison of serum amylase and blood calcium in each group(x ±s)

组别	只数	淀粉酶(U/L)					血钙(mmol/L)
组别	只数	6 h	12 h	24 h	F值	P值	6 h	12 h	24 h	F值	P值
对照组	18	448.00±95.12	445.17±67.74	412.17±84.31	1.327	0.308	2.35±0.08	2.27±0.21	2.27±0.10	0.669	0.518
SAP组	18	2 666.83±328.01^a	3 627.67±229.53^ac	5 517.33±337.93^acd	114.500	＜0.001	2.09±0.05^a	1.92±0.08^ac	1.75±0.08^acd	28.067	＜0.001
AG490组	18	2 049.17±257.00^ab	2 915.00±188.42^abc	3 746.50±181.05^abcd	147.130	＜0.001	2.22±0.08^ab	2.10±0.06^abc	1.97±0.07^abcd	15.767	＜0.001
F值		129.213	541.207	784.972			18.787	10.742	61.517
P值		＜0.001	＜0.001	＜0.001			＜0.001	＜0.001	＜0.001
注：淀粉酶，F_时点=218.636，F_组间=1 191.202，F_交互=70.450，均P＜0.05；血钙，F_时点=21.143，F_组间=69.163，均P＜0.05，F_交互=2.466, P=0.076。与对照组比较，^aP＜0.05；与SAP组比较，^bP＜0.05；与同组6 h比较，^cP＜0.05；与同组12 h比较, ^dP＜0.05。

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表 2 各组大鼠血清TNF-α、IL-1、IL-6水平比较(x ±s, ng/L)

Table 2. Comparison of serum TNF-α, IL-1, and IL-6 levels in rats of each group(x ±s, ng/L)

组别	只数	TNF-α
组别	只数	6 h	12 h	24 h	F值	P值
对照组	18	89.33±5.39	86.67±8.29	85.00±4.05	0.601	0.567
SAP组	18	286.50±12.06^a	333.33±10.69^ac	445.67±35.68^acd	105.600	＜0.001
AG490组	18	145.17±9.60^ab	276.67±14.68^abc	406.33±18.40^abcd	406.350	＜0.001
F值		696.956	754.183	432.795
P值		＜0.001	＜0.001	＜0.001

组别	只数	IL-6
组别	只数	6 h	12 h	24 h	F值	P值
对照组	18	52.83±10.30	56.83±8.93	59.17±5.95	0.811	0.472
SAP组	18	321.17±6.62^a	371.50±22.90^ac	463.33±22.91^acd	76.511	＜0.001
AG490组	18	142.17±10.61^ab	251.33±15.53^abc	370.83±22.76^abcd	283.082	＜0.001
F值		1280.277	537.023	748.312
P值		＜0.001	＜0.001	＜0.001

组别	只数	IL-1
组别	只数	6 h	12 h	24 h	F值	P值
对照组	18	10.67±1.69	11.49±1.34	11.87±2.13	1.130	0.361
SAP组	18	87.00±10.41^a	126.47±8.15^ac	108.72±15.63^acd	16.427	＜0.001
AG490组	18	31.53±3.65^ab	73.17±11.42^abc	39.02±6.39^abcd	44.406	＜0.001
F值		224.934	299.837	155.154
P值		＜0.001	＜0.001	＜0.001
注：TNF-α，F_时点=384.992，F_组间=1 097.802，F_交互=121.961；IL-6，F_时点=282.182，F_组间=2 229.541，F_交互=75.289；IL-1，F_时点=48.709，F_组间=666.874，F_交互=13.290，均P＜0.05。与对照组比较，^aP＜0.05;与SAP组比较，^bP＜0.05;与同组6 h比较，^cP＜0.05;与同组12 h比较, ^dP＜0.05。

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