白细胞介素11调控大鼠NEC肠道增殖与凋亡的分子机制研究

目的研究白细胞介素11(IL-11)调控大鼠坏死性小肠结肠炎(NEC)肠道增殖与凋亡的分子机制研究。方法实验分为正常对照组、NEC组和IL-11治疗组。1.细胞凋亡(TUNEL)法检测IL-11对大鼠肠上皮细胞凋亡的影响。2.免疫组织化学法检测IL-11对Bax、Bcl-2和增殖细胞核抗原(PCNA)表达变化的影响。数据采用SPSS 13.0软件统计分析。细胞凋亡表达变化和病理图像分析MOD值的变化以均数±标准差(±s)表示,One-Way-ANOVA方差分析,P0.01表示差异有统计学意义。结果 1.细胞凋亡变化:正常对照组肠上皮细胞核为弱阳性;NEC组绝大部分细胞核呈棕色,为强阳性;IL-11治疗组大部分呈棕色,呈阳性。定量分析表明NEC时肠上皮细胞凋亡显著增加,IL-11能显著减少凋亡。2.免疫组织化学法定量:NEC时肠上皮细胞Bax表达增加,Bcl-2、PCNA表达下降,表明IL-11能显著下调Bax,上调PCNA、Bcl-2的表达,差异均有统计学意义(P0.01)。结论肠上皮细胞凋亡在NEC显著增加,外源性IL-11能显著减轻肠道损伤,促进修复。其机制与IL-11下调Bax,上调Bcl-2、PCNA的表达有关。     

肠道损伤与修复模型中PTEN、Lgr5和β-catenin的表达变化

目的 观察肠道损伤与修复模型中PTEN、Lgr5和β-catenin的表达变化,探讨其在肠道损伤和修复中的作用.方法 通过含6％O2的N2缺氧和4℃冷刺激制备新生大鼠坏死性小肠结肠炎(necrotizing enterocolitis,NEC)肠道损伤与修复模型.随机分为对照组和实验组,分别于制模后24、72、120 h获取末端回肠组织,利用Realtime PCR方法,测定组织匀浆中PTEN、Lgr5和β-catenin mRNA的表达水平.结果 成功制备新生大鼠NEC肠道损伤与修复模型.制模后24 h,实验组PTEN、Lgr5和β-catenin mRNA表达水平(7.564、4.23、4.864)均明显高于对照组(3.028、2.2、1.296),差异有统计学意义(P＜0.05).制模后72 h和120h,实验组上述三者表达水平(72 h:1.477、1.45、1.604;120 h:1.590、0.85、1.174)与对照组(72 h:2.340、2.21、2.487;120 h:1.855、1.73、2.718)比较,差异均无统计学意义.结论 含6％O2的N2缺氧和4℃冷刺激是制备肠道损伤与修复模型的可行条件.肠道损伤早期,PTEN、Lgr5和β-catenin mRNA表达水平增加,可能与促进肠道干细胞增殖有关.肠道损伤后期及修复期,三者表达较早期明显下降,可能与PTEN负性调节β-catenin活性、平衡干细胞增殖速度有关.     

Intestinal complications after antenatal fetoscopic laser ablation in twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) occurs in 9% of monochorionic twin pregnancies. An imbalanced blood flow across placental vascular communications produces a hypovolemic condition in the donor fetus and hypervolemia in the recipient fetus, leading to a variety of postnatal complications. We report 3 cases of intestinal injury in TTTS after fetoscopic laser ablation of the communicating vessels: 2 cases of intestinal atresia, and 1 case of necrotizing enterocolitis of 1 twin. Intestinal ischemic diseases have been reported after prenatal laser treatment in TTTS; with this report, we add 3 more cases.     

Toll-like receptor 4 plays a role in macrophage phagocytosis during peritoneal sepsis

Background

Peritoneal sepsis is a significant cause of mortality in infants with necrotizing enterocolitis, caused in part by impaired bacterial clearance. Recent studies have identified toll-like receptor-4 (TLR4) as a receptor for endotoxin (lipopolysaccharide [LPS]). We hypothesized that TLR4 regulates bacterial clearance from the peritoneal cavity and sought to investigate whether macrophage phagocytosis was involved.

Methods

Peritoneal sepsis was induced in mice expressing either functional TLR4 (TLR4-wild-type [WT]) or mutant TLR4 by intraperitoneal injection of either live Escherichia coli or LPS. Phagocytosis was assessed by measuring the uptake of opsonized red cells. To assess bacterial clearance, we irrigated peritoneal cavities of injected animals with saline and plated it on gram-negative selective media.

Results

LPS significantly increased the rate of phagocytosis by peritoneal macrophages from TLR4-WT mice, but not in those from TLR4-mutant mice, suggesting a role for TLR4 in phagocytosis. LPS also increased the rates of phagocytosis in cultured macrophages expressing TLR4, confirming these findings. The yield of gram-negative bacteria obtained from the peritoneal cavities of septic TLR4-WT mice was greater than that from TLR4 mutants, consistent with TLR4-dependent alterations in their septic course.

Conclusions

We conclude that TLR4 plays a critical role in the response to intraperitoneal E. coli through effects on phagocytosis by macrophages, suggesting the possibility of using TLR4 as a therapeutic target in diseases of peritoneal sepsis.     

Postoperative Hirschsprung's enterocolitis after minimally invasive Swenson's procedure

Background/Purpose

Our preferred minimally invasive technique of Swenson's procedure has evolved from laparoscopic (LapSwen) to Swenson's transanal pullthrough (SWAP). We studied the incidence of postoperative Hirschsprung's enterocolitis (HEC) over the past decade.

Methods and Materials

We retrospectively reviewed the charts of 52 children who had a primary Swenson's pullthrough procedure between 1995 and 2006. Two cohorts (25 LapSwen [1995-2000] and 27 SWAP [1998-2006]) were compared.

Results

Median ages of diagnosis were 13 days for LapSwen and 4 days for SWAP. Median age at surgery was 4.1 months for LapSwen and 3.3 months for SWAP. Postoperative HEC occurred in 12% (16% LapSwen, 7.4% SWAP). The incidence of Down's syndrome and preoperative HEC did not differ between the 2 cohorts. Three children with HEC were Clostridium difficile-positive. Long-term function in the 36 children older than 4 years was excellent in 22%, good in 50%, fair in 11% and poor in 17%.

Conclusion

Our incidence of postoperative HEC is low, and we have seen a trend toward fewer cases after the SWAP procedure. Early diagnosis, preoperative rectal irrigations, and routine postoperative anal dilatation may be contributing to the elimination of HEC as a significant risk after surgery for Hirschsprung's disease.     

新生儿坏死性小肠结肠炎X线诊断

_目的：总结分析新生儿坏死性小肠结肠炎（NEC）的 X 线表现,提高对新生儿 NEC 早期病变的认识。方法：搜集经 X 线和/或临床手术病理证实的 NEC 病例52例,回顾性分析其临床及 X 线表现,对其孕周、出生体重与 NEC 发病关系进行分析;同时对52例病例的 X 线表现进行随访跟踪。结果：本组52例中首次摄片表现为典型 NEC 28例,表现为早期 NEC 13例,疑似早期 NEC 11例。13例早期 NEC 二次复查痊愈7例,进展为典型 NEC 4例,演变为肠道动力性异常2例。11例疑似早期 NEC 患儿第三次复查痊愈8例,进展为动力性梗阻3例,该3例第四次复查1例痊愈,2例出现典型 NEC 表现。结论：早产、低出生体重新生儿是 NEC 高危人群。X 线早期诊断对指导临床治疗及预后评估具有重要价值。     

早产单绒毛膜双胎新生儿坏死性小肠结肠炎临床特点分析及相关文献复习

目的 探讨单绒毛膜双胎(MCT)早产儿罹患坏死性小肠结肠炎(NEC)的临床特点。方法 选择2021年2月11日与1月18日,于青岛大学附属医院采取剖宫产术分娩的2例MCT罹患NEC女性早产儿(No.1、2患儿,均系MCT之小)为研究对象。采用回顾性研究方法,收集No.1、2患儿的临床病例资料,并对其临床表现、诊治进行分析。以“twins”“twins pregnancy”“multiple pregnancy”“monochorionic twins”“neonatal necrotizing enterocolitis”“双胎”“双胎妊娠”“单绒毛膜双胎”“新生儿坏死性小肠结肠炎”为关键词,在PubMed、中国知网、万方数据知识服务平台中,检索MCT罹患NEC患儿诊治相关研究文献;文献检索时间设定为上述数据库建库至2021年8月。本研究经过本院伦理委员会批准(审批文号：QYFY WZLL 26856)。结果 (1)临床病例资料分析：No.1、2患儿均无双胎输血综合征(TTTS)及双胎反向动脉灌注序列征(TRAPS)等并发症。No.1患儿出生胎龄为34⁺⁵周,出生...     

益生菌防治新生儿坏死性小肠结肠炎机制研究进展

新生儿坏死性小肠结肠炎(necrotizing enterocolitis, NEC)是导致新生儿尤其是早产儿和低出生体重儿死亡的病因之一。NEC的发生与新生儿肠道菌群定植延迟和结构紊乱密切相关。近些年大量研究认为,益生菌可通过调节肠道菌群结构,增强肠道屏障功能,减少病原菌定植和迁移,同时促进新生儿肠道免疫细胞发育和功...