Interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway

Pancreatitis occurs when digestive enzymes are activated in the pancreas. Severe pancreatitis has a 10-30% mortality rate. No specific treatments for pancreatitis exist now. Here, we discovered that interleukin-22 (IL-22) may have therapeutic potential in treating acute and chronic pancreatitis. Wild-type and IL-22 knockout mice were equally susceptible to cerulein-induced acute and chronic pancreatitis, whereas liver-specific IL-22 transgenic mice were completely resistant to cerulein-induced elevation of serum digestive enzymes, pancreatic necrosis and apoptosis, and inflammatory cell infiltration. Treatment of wild-type mice with recombinant IL-22 or adenovirus IL-22 markedly attenuated the severity of cerulein-induced acute and chronic pancreatitis. Mechanistically, we show that the protective effect of IL-22 on pancreatitis was mediated via the induction of Bcl-2 and Bcl-X(L), which bind to Beclin-1 and subsequently inhibit autophagosome formation to ameliorate pancreatitis. In conclusion, IL-22 ameliorates cerulein-induced pancreatitis by inhibiting the autophagic pathway. IL-22 could be a promising therapeutic drug to treat pancreatitis.     

Senescence determines the fate of activated rat pancreatic stellate cells

In chronic pancreatitis (CP), persistent activation of pancreatic stellate cells (PSC) converts wound healing into a pathological process resulting in organ fibrosis. Here, we have analysed senescence as a novel mechanism involved in the termination of PSC activation and tissue repair. PSC senescence was first studied in vitro by establishing long‐term cultures and by applying chemical triggers, using senescence‐associated β‐Galactosidase (SA β‐Gal) as a surrogate marker. Subsequently, susceptibility of PSC to immune cell‐mediated cytolysis was investigated employing cocultures. Using the model of dibutyltin dichloride‐induced CP in rats, appearance of senescent cells was monitored by immunohistochemistry and immunofluorescence, and correlated with the progression of tissue damage and repair, immune cell infiltration and fibrosis. The results indicated that long‐term culture and exposure of PSC to stressors (doxorubicin, H₂O₂ and staurosporine) induced senescence. Senescent PSC highly expressed CDKN1A/p21, mdm2 and interleukin (IL)‐6, but displayed low levels of α‐smooth muscle actin. Senescence increased the susceptibility of PSC to cytolysis. In CP, the number of senescent cells correlated with the severity of inflammation and the extension of fibrosis. Areas staining positive for SA β‐Gal overlapped with regions of fibrosis and dense infiltrates of immune cells. Furthermore, a close physical proximity of immune cells and activated PSC was observed. We conclude that inflammation, PSC activation and cellular senescence are timely coupled processes which take place in the same microenvironment of the inflamed pancreas. Lymphocytes may play a dual‐specific role in pancreatic fibrogenesis, triggering both the initiation of wound healing by activating PSC, and its completion by killing senescent stellate cells.     

生长抑素联合泮托拉唑钠治疗重症急性胰腺炎的临床研究

目的:探讨生长抑素联合泮托拉唑钠治疗重症急性胰腺炎(SAP)的临床效果。方法:选取我院2011年1月至2014年1月收治的83例SAP患者,按随机数字表法分为两组,研究组42例,对照组41例。对照组患者在常规治疗基础上给予生长抑素治疗,研究组患者给予生长抑素联合泮托拉唑钠治疗。比较两组患者治疗疗效,并记录患者腹痛缓解时间、脱离呼吸机时间、肠道功能恢复时间、血淀粉酶恢复正常时间。结果:研究组总有效率为90.5%(38/42),明显高于对照组的75.6%(31/41),差异有统计学意义(P0.05);研究组患者腹痛缓解时间、脱离呼吸机时间、肠道功能恢复时间及血淀粉酶恢复正常时间均明显短于对照组(P0.05)。结论:生长抑素与泮托拉唑钠联合治疗SAP疗效显著,可有效改善患者临床症状,值得临床推广应用。     

参芪扶正注射液对大鼠重症急性胰腺炎的治疗作用

目的:研究参芪扶正注射液对重症急性胰腺炎(SAP)的治疗作用。方法:66只Wistar大鼠随机分为:SAP假手术组(SO组),SAP模型组(SAP组)和参芪扶正注射液治疗组(SQ组),胆胰管逆行注射50g.l~(-1)牛磺胆酸钠复制大鼠SAP模型。造模成功后2、4、8、12、24 h检测血清中TNF-α、IL-6和ALT水平,观察肝脏组织病理改变。结果:与SO组相比,SAP组及SQ组血清中TNF-α、IL-6和ALT水平明显升高(P<0.05)。与SAP组相比,从8 h开始SQ组血清中TNF-α、IL-6和ALT水平开始下降(P<0.05),两组的肝脏病理改变无统计学意义。结论:参芪扶正注射液可以降低SAP时血清中ALT、TNF-α和IL-6水平,但不能改善肝脏组织的病理损伤程度,对SAP的发生、发展可能有一定的预防作用。     

不同营养支持对急性重症胰腺炎的效果对比及对血清钙离子、hs-CRP、AMS、PCT的影响

摘要 目的：探讨不同营养支持对急性重症胰腺炎的效果对比及对血清钙离子、超敏C反应蛋白（hs-CRP）、淀粉酶（AMS）、降钙素原（PCT）的影响。方法：选择2015年1月到2020年12月在我院接受治疗的131例急性重症胰腺炎患者,采用随机数表法分为试验组（n=66）和对照组（n=65）。对照组给予肠外营养支持治疗,试验组给予肠内营养支持治疗。比较两组临床疗效、钙离子、hs-CRP、AMS、PCT、D-乳酸、二胺氧化酶（DAO）、内毒素、临床症状改善情况及不良反应发生情况。结果：治疗后,两组总有效率比较差异显著（P<0.05）;治疗前,试验组和对照组血清抑钙离子、hs-CRP、AMS、PCT比较无显著差异;治疗后,试验组和对照组血清hs-CRP、AMS、PCT随着时间的推移而降低,且试验组均低于对照组,血清钙离子随着时间的推移而升高,且试验组高于对照组,差异显著（P<0.05）;治疗前,试验组和对照组血清D-乳酸、DAO、内毒素比较无显著差异;治疗后试验组和对照组血清D-乳酸、DAO、内毒素随着时间的推移而降低,且试验组均低于对照组,差异显著（P<0.05）;试验组腹痛缓解、肠鸣音恢复、血淀粉酶恢复及尿淀粉酶恢复时间均显著低于对照组,差异显著（P<0.05）;两组不良反应总发生率分别为9.09%、15.38%（P>0.05）。结论：在急性重症胰腺炎患者中应用肠内营养支持效果显著,可有效改善血清钙离子、hs-CRP、AMS、PCT水平,且不良反应较低。     

白藜芦醇联合乌司他丁治疗急性胰腺炎的疗效分析

目的:观察白藜芦醇联合乌司他丁对大鼠急性胰腺炎(AP)的治疗效果。方法:将250只雄性Wister大鼠随机分为5组,分别为假手术(A)组、急性胰腺炎组(B组)、白藜芦醇组(C组)、乌司他丁组(D组)和白藜芦醇联合乌司他丁治疗组(C+D组)。制备各组AS大鼠模型,观察各组腹水量及血淀粉酶、脂肪酶、TNF-α、NF-κB、丙二醛(MDA)及超氧化物歧化酶(SOD)水平,并观察胰腺病理改变。结果:B组与A组相比,SOD水平明显降低(P<0.05),MDA水平明显升高(P<0.05);C、D及C+D组与B组相比,血清SOD水平明显升高(P<0.05),MDA水平明显降低(P<0.05);C+D组与C组、D组相比,血清SOD水平明显升高(P<0.05),血清MDA水平明显降低(P<0.05)。与B组比较,C和D组血淀粉酶、脂肪酶、TNF-α、病理学评分均降低,细胞超微结构损伤减轻,有显著性差异(P<0.05或P<0.01)。C+D组上述指标改善较C组和D组更明显,差异有显著性(P<0.05)。结论:乌司他丁、白藜芦醇通过升高SOD保护性因子、降低MDA损伤性因子,对急性胰腺炎有治疗作用,尤其在乌司他丁与白藜芦醇合用时效果更显著。     

急性坏死性胰腺炎大鼠胰腺外分泌细胞中hsp70基因的表达

给大鼠胆胰管内逆行注射牛磺胆酸钠制备急性坏死性胰腺炎动物模型,采用Ｎｏｒｔｈｅｒｎ杂交及免疫组织化学方法检测了ｈｓｐ７０基因在胰腺外分泌细胞中的表达。Ｎｏｒｔｈｅｒｎ杂交分析发现,术后１ｈ即出现ｈｓｐ７０ｍＲＮＡ的高表达,然后开始下降,术后８－１６ｈ恢复至对照组水平。免疫组织化学检测发现,术后１ｈ即可见明显的ＨＳＰ７０蛋白染色,２ｈ最强,然后开始减弱,一直持续至１６ｈ,仍高于对照组水平;阳性染色位于腺泡细胞顶部并呈大颗粒状,而基底部、细胞核及腺泡腔内未见阳性信号。推测急性胰腺炎时胰腺外分泌细胞高表达ｈｓｐ７０基因,可能与其参与大量合成的胰酶的转运及抑制胰酶激活等保护作用有关。     

连续性血液净化对重症胰腺炎患者炎症因子、内毒素及肠道黏膜屏障功能的影响

目的:研究连续性血液净化对重症胰腺炎患者炎症因子、内毒素及肠道黏膜屏障功能的影响。方法:选取2014年2月至2015年1月本院收治的86例重症胰腺炎患者,按照投硬币法分为观察组(43例)和对照组(43例)。对照组采取常规治疗,观察组在此基础上加以连续性血液净化治疗。比较两组患者治疗前后炎症因子、内毒素、肠道黏膜屏障功能变化情况,分析两组患者临床症状缓解时间。结果:治疗后,观察组血清白介素-6(IL-6)、白介素-8(IL-8)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、内毒素、D-乳酸、二胺氧化酶水平明显低于对照组(P0.05),压痛、腹痛、腹胀症状缓解时间显著短于对照组(P0.05)。结论:连续性血液净化能有效改善重症胰腺炎患者炎症因子水平、内毒素及肠道黏膜屏障功能,促进患者临床症状快速恢复。     

Effects of Modulation of the Activity of the Autonomic Nervous System on the Efficiency of Liposomal Sandostatin in the Treatment of Experimental Pancreatitis

We measured the concentrations of the main gastrointestinal hormones (gastrin, somatostatin, insulin, and glucagon) in the blood serum of control rats and rats with experimental chronic pancreatitis (EChP). The composition of gastrointestinal hormones in the blood of animals with EChP was shown to change considerably; this was manifested in increases in the contents of gastrin and glucagon and a dramatic drop in the insulin concentration. Injections of the liposomal form of sandostatin exerted a normalizing effect on the secretory activity of the gastroenteropancreatic axis. The liposomal sandostatin-induced normalization of the composition of gastrointestinal hormones was more significant in animals with EChP, which were bilaterally vagotomized; pharmacological desympathization did not exert a considerable effect on the curative activity of sandostatin.