Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22

BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.

Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis

AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.

Interleukin-22 ameliorates acute severe pancreatitisassociated lung injury in mice

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P < 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.

Interleukin-22 contributes to liver regeneration in micewith concanavalin A-induced hepatitis after hepatectomy

AIM: To investigate the therapeutic effects and mechanisms of interleukin(IL)-22 in liver regeneration in mice with concanavalin A(Con A)-induced liver injury following 70% hepatectomy.METHODS: Mice were injected intravenously with Con A at 10 μg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 μg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline.RESULTS: IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3(STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein m RNA expression was significantly elevated after IL-22 treatment.CONCLUSION: In this study, we demonstrated that IL-22 is a survival factor for hepatocytes and prevents and repairs liver injury by enhancing pro-growth pathways via STAT3 activation. Treatment with IL-22 protein may represent a novel therapeutic strategy for preventing liver injury in patients with liver disease who have undergone hepatectomy.

Interleukin-22 receptor 1 is expressed in multinucleated giant cells:A study on intestinal tuberculosis and Crohn’s disease

BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.

Role of interleukin-22 in inflammatory bowel disease

Inflammatory bowel disease(IBD)is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses.Aberrant immune responses can cause secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract,leading to further inflammation.Interleukin(IL)-22 is a member of the IL-10 family of cytokines that was recently discovered to be mainly produced by both adaptive and innate immune cells.Several cytokines and many of the transcriptional factors and T regulatory cells are known to regulate IL-22 expression through activation of signal transducer and activator of transcription 3signaling cascades.This cytokine induces antimicrobial m olecules and proliferative and antiapoptoic pathways,which help prevent tissue damage and aid in its repair.All of these processes play a beneficial role in IBD by enhancing intestinal barrier integrity and epithelial innate immunity.In this review,we discuss recent progress in the involvement of IL-22in the pathogenesis of IBD,as well as its therapeutic potential.

Mechanisms of interleukin-22's beneficial effects in acutepancreatitis

Acute pancreatitis(AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin(IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly antiinflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the antiautophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy.

The Expression of Interleukin-22 and S100A7, A8, A9 mRNA in Patients with Psoriasis Vulgaris

In order to study the expression of interleukin-22 （IL-22） and S 100A7, A8, A9 mRNA in the skin lesions of patients with psoriasis vulgaris and their relationship, the biopsies were taken from skin lesions in 35 patients with psoriasis vulgaris and the skin of 16 normal controls, and the expression levels of 1L-22 and S 100A7, A8 and A9 mRNA were detected by semi-quantitative RT-PCR. The results showed that （1） IL-22 and S 100A8, A9 mRNA were positively expressed in the psoriatic skin lesions but negatively expressed in the normal controls; The expression level of S 100A7 was （1.133±0.040） in the psoriatic skin lesions, significantly higher than that in the normal controls （0.744±0.037, P〈0.01）. （2） There were significantly positive correlations between the expression of IL-22/S100A7 mRNA, IL-22/S100A8 mRNA, IL-22/S100A9 mRNA in the psoriasis vulgaris （r1=-0.543, r2=0.774, r3=0.621, P〈0.01）. It was concluded that IL-22 and S 100A7, A8, A9 might play important roles in the occurrence and progression of psoriasis.

Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines

AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.

Interleukin-22 regulating fibrosis on mouse cardiac fibroblasts through STAT3 signaling pathway

Objective:To observe the effects of interleukin-22(IL-22)on the expression of type Ⅲ collagen,cytokines,growth factors and chemokines in mouse cardiac fibroblasts in vitro.Methods:Mouse cardiac fibroblasts were treated with0μg/L(control),1μg/L(low concentration)and 100μg/L(high concentration)IL-22,respectively.In addition,cells treated with 100μmol/L static(an STAT3 pathway inhibitor)and 100μg/L IL-22 was defined as the block group.After treatment for 48 hours,the mRNA level of collagen type Ⅲ A1(Col3-A1),matrix metalloproteinase-1(Timp-1),IL-22receptor(IL-22R),interleukin 10-related T cellderived inducible factor beta(Iltifb),fibroblast growth factor1(Fgf1)and C-C motif chemokine ligand 4(Ccl4)were determined by RT-PCR.The expression of Col3-A1 in cardiac fibroblasts was also semi-quantified by immunofluorescence.Results:Expression of Col3-A1 decreased in the low and high concentration groups,but significantly increased in the block group(all P <0.05).The expression of Timp-1increased in the low,high concentration and block groups compared with that in the control group,but it was significantly lower in the high concentration group than that in the low concentration group(P <0.05).The expression of IL-22 Rand Iltifb was significantly increased in the low,high concentration and block groups compared with that in the control group(P <0.05),but there was no statistical difference between the high concentration group and block group.The expression of Fgf1 and Ccl4 was significantly decreased in the low,high concentration and block groups compared with that in the control group(P <0.05),but there was no statistic difference between the high concentration group and block group as well.Conclusion:IL-22 effected on the expression of Col3-A1 and Timp-1,which was possibly through the JAK-STAT3 signaling pathway in mice cardiac fibroblasts.

白细胞介素-22在神经系统疾病中的研究进展

白细胞介素-22(IL-22)是炎症和感染过程中免疫细胞向组织传递信号的重要介质,在炎症中发挥双重作用。在急性感染中,短期内IL-22具有的促进细胞增殖、抑制细胞凋亡、增加黏蛋白和抗菌肽产生等能力对宿主有益;在慢性感染中,细胞增殖过度和凋亡减少可导致异常增生。IL-22可通过Janus激酶/信号转导及转录活化因子等信号通路参与缺血性脑卒中、胶质瘤等神经系统疾病的调节,可作为未来神经系统疾病调控的一个新的、可持续的研究方向,为疾病的治疗提供精准的靶点和新的策略。

重组白细胞介素-22通过抑制炎症因子表达减缓肝纤维化的实验研究

目的 观察重组白细胞介素(IL)-22通过抑制炎症因子表达对肝纤维化小鼠的影响。方法 选取16只6周龄雄性BABL/c小鼠,均腹腔注射20%四氯化碳造模,2次/周,在造模后第8周,将小鼠随机分成重组IL-22组(n=8)和对照组(n=8)。重组IL-22组和对照组小鼠分别腹腔注射0.3μg/g重组IL-22和等体积0.5%牛血清白蛋白(以磷酸盐缓冲液为溶剂,pH 7.0),1次/d,直到第10周处死小鼠。通过苏木精-伊红(HE)和Masson染色了解两组小鼠的肝脏病理改变,根据Ishak评分系统评估两组小鼠的肝纤维化程度;利用免疫组织化学法检测肝脏组织中α-平滑肌肌动蛋白(α-SMA)、IL-22的表达;采用流式细胞仪检测两组小鼠脾脏Th22细胞数的变化;采用实时荧光定量PCR法检测肝脏组织IL-22R1、IL-10R2、IL-22、IL-17A、IL-6和肿瘤坏死因子(TNF)-α mRNA的表达,采用ELISA法检测血浆中IL-22、 IL-17A、IL-6和TNF-α蛋白表达水平。结果 (1)HE和Masson染色结果显示,重组IL-22组小鼠肝脏组织的炎症、坏死和纤维化程度较对照组小鼠明显减轻,Ishak评分较对照组小鼠下降(P<0.05)。(2)重组IL-22组小鼠肝脏组织α-SMA的蛋白表达水平,以及肝脏组织和血浆中IL-22的表达水平均明显低于对照组(均P<0.05)。(3)重组IL-22组小鼠脾脏组织Th22细胞百分比和肝脏组织IL-22、IL-22R1、IL-10R2的mRNA表达水平均低于对照组(均P<0.05)。(4)重组IL-22组小鼠肝脏组织IL-17A、IL-6和TNF-α的mRNA表达水平,以及血浆IL-22、IL-17A、IL-6和TNF-α的蛋白表达水平均低于对照组(均P<0.05)。结论 重组IL-22可减缓肝纤维化,其作用机制可能与其减弱肝星状细胞的活性和下调炎症因子的水平有关。

白细胞介素-17和白细胞介素-22在大疱性类天疱疮患者皮损及血清中的表达与意义

目的检测分析大疱性类天疱疮(BP)患者皮损及血清中白细胞介素(IL)-17和IL-22的表达情况,并探讨其在BP发病机制中的意义。方法选取41例BP患者皮损组织(BP组)及25名健康人正常皮肤组织(对照组),用免疫组化方法检测IL-17和IL-22的表达情况。采用酶联免疫吸附试验(ELISA)检测27例BP患者血清中IL-17和IL-22的水平,并以25名健康人作为对照。结果BP组患者皮损中IL-17和IL-22的表达均明显高于对照组,差异有统计学意义(均P<0.01)。且BP组患者皮损组织中IL-17与IL-22的表达呈正相关性。BP组患者血清中IL-17和IL-22的表达水平均高于对照组,差异有统计学意义(均P<0.01)。BP组患者血清中IL-17与IL-22的表达呈正相关性。结论BP患者血清及皮损IL-17和IL-22的表达水平上调,可能参与BP的发病,且两者可能起协同作用。提示3型固有淋巴细胞(ILC3)可能参与BP的致病过程。

血清miR-31、IL-22联合检测在儿童病毒性心肌炎诊断及预后评估中的价值

目的 研究血清微小RNA-31(miR-31)、白细胞介素-22(IL-22)在儿童病毒性心肌炎(VMC)诊断及预后评估中的价值。方法 选取2017年1月至2022年1月河南省儿童医院心血管内科收治的病毒性心肌炎患儿作为研究对象,将其命名为VMC组(n=106),另选同期在本院进行体检的健康儿童为对照组(n=70)。比较两组血清miR-31、IL-22、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白T(cTnT)及心电图参数[QRS间期、PR间期]与超声心动图参数[左室射血分数(LVEF)、左心室短轴缩短率(LVFS)];在治疗结束后对VMC患儿随访1年,以随访期间发生恢复迁延、扩张性心肌病、遗留心律失常及患儿死亡等事件为预后不良,根据多因素Logistic回归分析VMC患儿预后不良的影响因素,并绘制ROC曲线分析血清miR-31、IL-22水平对VMC患儿诊断及预后不良评估的价值。结果 VMC组的血清miR-31、IL-22、CK-MB、cTnT水平及QRS间期、PR间期均高于对照组,差异有统计学意义(P<0.05),LVEF、LVFS均低于对照组,差异有统计学意义(P<0.05);多因素Logistic回归分析显示,miR-31水平高表达、IL-22水平升高、CK-MB水平升高、cTnT水平升高、QRS间期延长、PR间期延长、LVEF降低及LVFS降低均是VMC患儿预后不良的独立危险因素(P<0.05);ROC曲线分析显示,血清miR-31、IL-22水平二者联合检测诊断VMC的曲线下面积(AUC)为0.990,优于单一检测(P<0.05);血清miR-31、IL-22水平二者联合检测评估VMC患儿预后不良的曲线下面积(AUC)为0.919,优于单一检测(P<0.05)。结论 miR-31、IL-22在病毒性心肌炎患儿血清中高表达,可能成为儿童病毒性心肌炎诊断及预后评估的辅助诊断指标。

HPVL1蛋白、TRIM22、HER-2联合检测在HPV阳性宫颈上皮内瘤变中的早期诊断价值

目的 探讨人乳头瘤病毒LI(HPVL1)蛋白、三结构域家族蛋白22(TRIM22)、人表皮生长因子受体-2(HER-2)联合检测在人乳头瘤病毒(HPV)阳性宫颈上皮内瘤变(CIN)中的早期诊断价值。方法 回顾性选取2021年1月至2023年6月承德医学院附属医院就诊的162例薄层液基细胞学(TCT)检查异常且HPV阳性的CIN患者为研究组,另选取同期经组织病理学诊断为正常宫颈组织的138名对象为对照组。免疫组织化学法检测宫颈组织中HPVL1蛋白、TRIM22、HER-2表达。比较对照组、研究组组织中HPVL1蛋白、TRIM22、HER-2表达,并比较不同分级CIN患者HPVL1蛋白、TRIM22、HER-2表达。多因素Logistic回归模型分析CIN发生的影响因素;受试者操作特征(ROC)曲线分析HPVL1蛋白、TRIM22、HER-2表达对CIN的早期诊断价值。结果 研究组组织中HPVL1蛋白及TRIM22蛋白阳性率分别为34.57%、32.72%,均显著低于对照组(74.64%、71.01%),HER-2阳性率为60.49%,显著高于对照组(10.87%),差异均有统计学意义(P<0.05)。CINⅠ级、CINⅡ级和CINⅢ级HPVL1蛋白和TRIM22阳性率呈下降趋势,HER-2阳性率呈上升趋势(P<0.05)。多因素Logistic回归分析结果显示,宫颈组织中HPVL1蛋白、TRIM22及HER-2表达均为CIN的影响因素(OR=5.110、5.231、9.652,P<0.05)。ROC曲线结果显示,HPVL1蛋白表达诊断CIN的曲线下面积(AUC)为0.700,敏感度为65.43%;TRIM22表达诊断CIN的AUC为0.691,敏感度为67.28%;HER-2表达诊断CIN的AUC为0.748,敏感度为60.49%。三者联合诊断CIN的AUC为0.814,显著高于单独诊断的AUC(P<0.05)。结论 宫颈组织中HPVL1蛋白、TRIM22及HER-2表达影响CIN的发生、发展,三者联合对CIN具有较高的诊断价值。

姜酮通过激活Nrf2/HO-1信号通路减轻OGD/R后氧化应激损伤对HT22细胞凋亡的抑制作用

目的:探讨姜酮对氧糖剥夺/复糖复氧(OGD/R)后小鼠海马神经元HT22细胞的保护作用,阐明其相关作用机制。方法:培养HT22细胞,设置不同OGD/R时间梯度,建立OGD/R细胞损伤模型。HT22细胞分为对照组、OGD/R组、OGD/R+1μmol·L^(-1)姜酮组、OGD/R+10μmol·L^(-1)姜酮、OGD/R+100μmol·L^(-1)姜酮组和OGD/R+0.2%二甲亚枫(DMSO)组,CCK-8法检测各组细胞活性并计算各组细胞存活率,确定姜酮最适药物浓度。细胞分为对照组、OGD/R组、OGD/R+姜酮组和OGD/R+姜酮+核因子E2相关因子2(Nrf2)抑制剂(ML385)组,OGD/R+姜酮组细胞经姜酮给药处理4 h后予以OGD 8 h和复糖复氧8 h处理,OGD/R+姜酮+ML385组细胞在姜酮给药前予以10μmol·L^(-1)ML385预处理6 h,CCK-8法检测各组细胞活性,Western blotting法检测各组细胞中Nrf2、血红素加氧酶1(HO-1)、B细胞淋巴瘤2(Bcl-2)和Bcl-2相关X蛋白(Bax)蛋白表达水平,酶联免疫吸附试验(ELISA)法检测各组细胞培养上清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平。结果:与对照组比较,HT22细胞经OGD 8 h和复糖复糖8 h处理后细胞存活率低于50%,以OGD 8 h和复糖复糖8 h建立HT22细胞OGD/R模型。与OGD/R组比较,OGD/R+不同剂量姜酮组细胞存活率均不同程度升高,其中OGD/R+100μmol·L^(-1)姜酮组细胞存活率升高最明显(P<0.01),故选用100μmol·L^(-1)姜酮用于后续实验。与对照组比较,OGD/R组细胞活性明显降低(P<0.01),细胞中Nrf2、HO-1和Bax蛋白表达水平明显升高(P<0.01),Bcl-2蛋白表达水平明显降低(P<0.05),细胞培养上清中SOD活性明显降低(P<0.01),MDA水平明显升高(P<0.01);与OGD/R组比较,OGD/R+姜酮组细胞活性明显升高(P<0.01),细胞中Nrf2、HO-1和Bcl-2蛋白表达水平明显升高(P<0.05或P<0.01),Bax蛋白表达水平明显降低(P<0.05),细胞培养上清中SOD活性明显升高(P<0.01),MDA水平明显降低(P<0.01);与OGD/R+姜酮组比较,OGD/R+姜酮+ML385组细胞活性明显降低(P<0.01),细胞中Nrf2、HO-1和Bcl-2蛋白表达水平明显降低(P<0.01),Bax蛋白表达水平明显升高(P<0.01),细胞培养上清中SOD活性明显降低(P<0.01),MDA水平明显升高(P<0.05)。结论:姜酮可通过激活Nrf2/HO-1信号通路减轻OGD/R后氧化应激损伤对HT22细胞凋亡的抑制作用。

急性胰腺炎患者血清CXC趋化因子配体10和CC类趋化因子22水平与疾病严重程度关系及临床诊断价值研究

目的:分析急性胰腺炎患者血清CXC趋化因子配体10(CXCL10)和CC类趋化因子22(CCL22)水平与疾病严重程度的关系及临床诊断价值。方法:选取急性胰腺炎患者102例,分为轻症组(轻症急性胰腺炎患者,47例)、中度重症组(中度重症急性胰腺炎患者,31例)和重症组(重症急性胰腺炎患者,24例)。选择52例体检健康者为健康组。采用全自动生化分析仪检测受试者肝功能指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)]、肾功能指标[肌酐(Scr)、血尿素氮(BUN)]以及淀粉酶(AMY)水平。采用酶联免疫吸附法检测血清中CXCL10、CCL22水平。采用急性胰腺炎严重程度床边指数(BISAP)评分评估急性胰腺炎患者疾病严重程度。采用Logistic回归分析中度重症和重症急性胰腺炎发生的影响因素。采用Pearson法分析急性胰腺炎患者血清CXCL10、CCL22水平及BISAP评分间的相关性。采用受试者工作特征(ROC)曲线评价血清CXCL10、CCL22水平诊断中度重症和重症急性胰腺炎的价值。结果:与健康组比较,轻症组ALT、Scr、BUN、AMY水平升高,中度重症组和重症组ALT、AST、Scr、BUN、AMY水平升高(均P<0.05)。与轻症组比较,中度重症组BUN水平升高,重症组ALT、AST、Scr、BUN水平升高(均P<0.05)。与中度重症组比较,重症组BUN水平升高(P<0.05)。四组血清CXCL10、CCL22水平及BISAP评分依次升高(均P<0.05)。急性胰腺炎患者血清CXCL10和CCL22水平呈正相关(P<0.05);血清CXCL10、CCL22水平与BISAP评分呈正相关(均P<0.05)。血清CXCL10、CCL22、BISAP评分是中度重症和重症急性胰腺炎发生的独立危险因素(均P<0.05)。血清CXCL10、CCL22对中度重症和重症急性胰腺炎均有一定诊断价值,且两项联合诊断价值更高(均P<0.05)。结论:急性胰腺炎患者血清CXCL10、CCL22水平呈高表达,且随疾病严重程度的加重而升高,两者联合诊断中度重症和重症急性胰腺炎的价值较高。

不同Hp感染的老年慢性胃炎患者miR-22、MIF、IFN-γ蛋白表达及意义

目的研究分析不同幽门螺旋杆菌(Hp)感染状态和不同病理类型老年慢性胃炎患者中微小核糖核酸-22(miR-22)、巨噬细胞移动抑制因子(MIF)及γ-干扰素(IFN-γ)蛋白的表达及意义。方法收集2021年1月至2023年12月大庆油田总医院收治的98例慢性胃炎患者的临床资料进行回顾性分析,根据患者是否Hp感染分为Hp阳性组(n=41)及Hp阴性组(n=57),根据病例类型将患者分为慢性萎缩性胃炎(CAG)组(n=55)与慢性非萎缩性胃炎(CNAG)组(n=43)。观察不同病理类型患者Hp感染情况,并比较不同Hp感染情况、不同病理类型中老年慢性胃炎患者miR-22、MIF、IFN-γ蛋白表达水平的差异。结果CAG患者的Hp阳性率高于CNAG患者(P<0.05);相较于CNAG组,CAG组miR-22表达明显降低(P<0.05),而MIF mRNA及IFN-γ蛋白均明显升高(P<0.05);相较于Hp阴性组,Hp阳性组miR-22表达明显降低(P<0.05),而MIF mRNA及IFN-γ蛋白均明显升高(P<0.05);Hp阳性并CAG组miR-22表达明显低于Hp阳性并CNAG组、Hp阴性并CAG组及CNAG组(P<0.05),而MIF mRNA及IFN-γ蛋白明显高于Hp阳性并CNAG组、Hp阴性并CAG组及CNAG组(P<0.05)。结论Hp感染状态的老年慢性胃炎患者存在miR-22、MIF、IFN-γ蛋白含量表达异常,上述分子标志物反映患者胃黏膜的炎症程度、细胞增生和凋亡的失衡,同时miR-22、MIF、IFN-γ蛋白的表达模式反映病理变化的严重性,影响CAG的发生。

苗药黑骨藤对CIA大鼠外周血Th22细胞数量及血清IL-17、IL-22和IL-35表达水平的影响

目的观察苗药黑骨藤对CIA大鼠外周血Th22细胞数量和细胞因子IL-17、IL-22和IL-35的表达水平的影响。将60只CIA大鼠作为研究对象,按随机数字表法随机分为正常对照组、模型对照组、阳性对照组(雷公藤多苷,9.45mg/kg)、黑骨藤低剂量组(22 mg/kg)、中剂量组(44 mg/kg)和高剂量组(67 mg/kg),每组10只。建立大鼠CIA模型,连续给药21 d后测定大鼠血清IL-17、IL-22、IL-35水平和Th22细胞数量,观察大鼠足趾组织镜下表现。结果与模型对照组比较,阳性对照组、黑骨藤低剂量组、剂量组血清、高剂量组血清IL-17、IL-22水平以及Th22细胞比例明显降低,血清IL-35水平明显增高,黑骨藤高剂量组在降低血清IL-17、IL-22水平,升高血清IL-35水平效果上优于阳性对照组。结论黑骨藤可以减少Th22细胞数量,调节IL-17、IL-22、IL-35等细胞因子表达,具有减少炎症细胞活化和浸润、抑制关节炎症的作用,从而减缓类风湿关节炎的进展。

消结化瘤汤对子宫肌瘤患者血清性激素和IL-22、TNF-α水平的影响

目的:探讨消结化瘤汤对子宫肌瘤(UM)患者血清性激素和白介素-22(IL-22)、肿瘤坏死因子-α(TNF-α)水平的影响。方法:选取2020年1月~2022年12月本院收治的112例血瘀型UM患者,采用随机数字表法分为观察组和对照组各56例。对照组给予米非司酮片口服治疗,观察组在对照组治疗基础上给予消结化瘤汤,两组均连续治疗3个月。比较两组临床疗效及治疗前后中医证候积分、血清雌二醇(E2)、孕酮(P)、卵泡刺激素(FSH)、促黄体生成素(LH)、IL-22、TNF-α水平和治疗期间不良反应发生率。结果:观察组治疗总有效率为87.50%,显著高于对照组的71.43%(P<0.05);观察组治疗后各项中医症候积分显著低于对照组(P<0.05);观察组E2、P、LH、FSH水平均显著低于对照组(P<0.05);观察组血清IL-22、TNF-α等指标改善程度显著高于对照组(P<0.05);观察组治疗期间不良反应发生率为17.86%,与对照组的16.07%无显著差异(P>0.05)。结论:消结化瘤汤可有效改善血瘀型UM患者血清性激素水平,降低IL-22、TNF-α水平。