A型肉毒毒素治疗挛缩性瘢痕的初步研究

目的：探讨A型肉毒毒素（BTXA）治疗挛缩性瘢痕的效果及其作用机制.方法：10例烧伤后挛缩性瘢痕患者,每人选取两处挛缩性瘢痕,随机分为BTXA组（瘢痕内注射BTXA,间隔3个月1次,共2次）和空白对照组（瘢痕内注射等积生理盐水）,于注射前及首次注射后1、3、6个月测量瘢痕长轴长度,观察其长度变化用以反映瘢痕挛缩程度;切取5例药物治疗6个月后行瘢痕切除手术患者的瘢痕组织,HE染色观察病理学改变,免疫组化染色观察α-平滑肌肌动蛋白及肌球蛋白-Ⅱ的表达.结果：BTXA组较空白对照组瘢痕挛缩程度明显减轻（P〈0.01）,尤以6个月时差异明显[（1.103±0.158）cm比（0.187±0.221）cm].常规HE染色观察到BTXA组瘢痕组织内胶原纤维排列稀疏且规则,瘢痕内成纤维细胞数量较空白对照组减少.免疫组化结果显示BTXA组瘢痕内α-平滑肌肌动蛋白及肌球蛋白-Ⅱ表达较空白对照组明显减少（P〈0.01）.结论：BTXA可用于治疗挛缩性瘢痕,作用机制可能与BTXA能够抑制瘢痕内成纤维细胞中α平滑肌肌动蛋白及肌球蛋白-Ⅱ的表达有关.     

连续Y-V成形术联合糖皮质激素及A型肉毒毒素注射治疗瘢痕挛缩畸形

目的:研究Y-V成形术联合糖皮质激素及A型肉毒毒素注射治疗瘢痕挛缩的效果,分析连续的Y-V成形术应用于瘢痕挛缩的原理。方法:本组共46例瘢痕挛缩患者,随机分为观察组和对照组,每组23例,对照组采用单纯的连续Y-V成形术治疗,观察组采用连续的Y-V成形术联合糖皮质激素及A型肉毒毒素局部注射治疗,比较两组临床疗效及不良反应发生情况。应用数学模型阐述连续的Y-V成形术治疗挛缩瘢痕的基本原理,用三角函数论证相关参数的关系,分析影响瘢痕挛缩治疗效果的因素。结果:观察组总有效率为86.9%高于对照组的56.5%,且观察组术后关节活动度改善度为(9.48±3.34)°高于对照组的(7.43±1.49)°,差异均有统计学意义(P0.05)。两组间不良反应发生率比较差异无统计学意义(P0.05)。结论:Y-V成形术联合糖皮质激素及A型肉毒毒素注射治疗瘢痕挛缩效果显著,操作简单,并发症少,值得推广应用。     

A型肉毒毒素预防与治疗早期增生性瘢痕的临床初探

目的 探索A型肉毒毒素(botulinum toxin type A,BTXA)对早期增生性瘢痕(hypertrophic scar,HTS)的临床预防及治疗效果.方法 早期HTS周围及组织内注射BTXA,观察瘢痕注射药物后形态学变化、组织学变化及临床症状表现;手术切口缝合后即刻向周围肌肉浅层注射BTXA,观察远期瘢痕愈合情况.结果 局部注射BTXA可以明显减轻早期HTS疼痛和瘙痒症状,促使瘢痕组织萎缩、软化;组织切片HE染色显示HTS组织内结构有所变化.同时,手术切口周围肌肉浅层注射BTXA可以降低术后切口HTS的发生、发展概率.结论 BTXA对早期HTS具有一定程度的治疗和预防作用,其疗效可能是通过降低瘢痕两侧张力及活动,干扰瘢痕内小神经传导,以及影响成纤维细胞增殖分化,促进凋亡进而减少胶原合成而起作用.     

人咬肌内注射A型肉毒毒素后收缩蛋白变化的免疫组化观察

目的观察人咬肌内注射A型肉毒毒素后肌动蛋白和肌球蛋白的变化。方法共收集60份良性咬肌肥大患者的咬肌标本,对照组30份未注射A型肉毒毒素,实验组30份已注射A型肉毒毒素。2组标本均采用免疫组织化学染色法,光镜下观察标本中肌动蛋白和肌球蛋白的表达情况,测量其光密度值并进行统计学分析。结果实验组肌动蛋白和肌球蛋白的表达下降,其中以肌动蛋白下降显著,与对照组相比,其差异具有统计学意义(P0.05)。肌动蛋白和肌球蛋白的表达在第12周时下降最显著,之后表达逐渐恢复,至第24周时肌动蛋白和肌球蛋白的表达与对照组比较,其差异无统计学意义(P0.05)。结论人咬肌内注射A型肉毒毒素致咬力降低的临床现象为A型肉毒毒素影响咬肌收缩蛋白的表达。     

A型肉毒毒素对兔植皮后皮片收缩相关因素的影响

／目的研究A型肉毒毒素对兔植皮术后皮片收缩的相关因素影响。方法于兔背部沿脊柱两侧对称地制备两排共4个2cm×2cm正方形供皮区,切取全厚皮片,共形成20个创面。每只兔背部随机选取2个创面皮下注射A型肉毒毒素5U,此为A组,共10个创面;其余未注射A型肉毒毒素的创面为B组。术后12d,大体观察切口愈合及植皮成活情况。观察组织的HE染色标本中炎症细胞、成纤维细胞、胶原纤维的变化及免疫组织化学染色标本中α-SMA表达;测量每张图片α-SMA的积分光密度值。结果大体观察A组与B组切口愈合及皮片成活无明显差异。光镜下,观察A组较B组真皮中炎症细胞减少,胶原纤维相对细小、致密度下降,排列较规则,大体走向一致;成纤维细胞数量减少,较分散。A组与B组α-SMA的积分光密度值组间差异具有统计学意义（P=0．003）,A组α-SMA的表达较B组明显减少。结论A型肉毒毒素的注射不影响植皮的正常成活及切口愈合。可通过减少收缩过程中的成纤维细胞的数量、胶原的合成与沉积及炎症细胞的生成,以减少肌成纤维细胞中α-SMA的表达,达到抑制皮片收缩的目的。     

A型肉毒毒素对瘢痕疙瘩成纤维细胞TGF-β/Smad通路和ERK通路表达的影响

目的:探讨A型肉毒毒素对人瘢痕疙瘩成纤维细胞(Human keloid fibroblasts,HKF)生物学行为和TGF-β/Smad信号通路和ERK信号通路表达的影响。方法:在HKF培养过程中加入A型肉毒毒素进行干扰,观察A型肉毒毒素对瘢痕疙瘩成纤维细胞TGF-β/Smad通路和ERK通路相关分子的变化及细胞增殖、侵袭、凋亡情况。结果:A型肉毒毒素可以抑制HKF增殖、迁移和侵袭,促进凋亡,并且明显抑制Ⅰ型胶原、Ⅲ型胶原、纤维连接蛋白、α-SMA和CTGF基因的表达水平,上调IFN-γ、TGF-β3基因的表达水平。上调Smad7基因和蛋白的表达,下调VEGF基因表达,明显抑制p-Smad2和p-Smad3蛋白表达水平,并且抑制P-ERK1/2蛋白表达。以上生物学变化均且呈药物浓度依赖性。结论:A型肉毒毒素可抑制HKF的增殖、侵袭、血管生成和胶原积累,这些效应与TGF-β/Smad和ERK1/2信号通路有关。     

A型肉毒毒素联合复方倍他米松治疗大面积增生性瘢痕的临床疗效观察

目的探讨A型肉毒毒素联合复方倍他米松治疗大面积增生性瘢痕的临床效果。方法回顾性分析2017年3月至2019年3月于北部战区总医院烧伤整形科收治的39例大面积增生性瘢痕患者的临床资料,根据采用的治疗方法分为A组:A型肉毒毒素联合复方倍他米松瘢痕内注射组(13例);B组:A型肉毒毒素瘢痕内注射组(12例);C组:复方倍他米松瘢痕内注射组(14例)。记录治疗的总有效率,参照温哥华瘢痕评分量表(vancouver scar score sheet,VSS)对3组患者的瘢痕色泽、血管分布、柔软度进行综合评分;采用彩色多普勒超声诊断仪测量瘢痕厚度,并参照视觉模拟评分量表(visual analogue scale,VAS)评价患者的痛痒觉改善情况;记录不良反应发生情况;随访6个月。结果A组的总有效率(92.31%)、VSS值、瘢痕厚度、VAS值评价均明显优于B组(75.00%)和C组(50.00%),其差异有统计学意义(P<0.05)。A、B组经3次治疗后,痛痒症状明显缓解,病情趋于稳定。治疗6个月随访时A组患者未再复发,B组复发2例。3组中有极个别患者在治疗后偶发针孔周围皮肤红肿,于1~2 d自行缓解,未发生严重的不良反应。结论A型肉毒毒素联合复方倍他米松治疗大面积增生性瘢痕安全有效,能提高单次治疗的有效面积及效果并减少激素用量及其并发症,值得临床推广应用。     

大剂量A型肉毒毒素局部注射治疗腋部多汗症

目的 探讨大剂量肉毒毒素治疗腋部多汗症的长期疗效和重复治疗的疗效.方法 92例患者随机分为两组:小剂量组为每侧腋部皮内注射生理盐水稀释的A型肉毒毒素50U;大剂量组为每侧腋部皮内注射生理盐水稀释的A型肉毒毒素200U;随访3～29个月,观察两组并发症,并建立两组等级资料,经χ2 检验,评价两组患者疗效差异.结果 两组疗效进行对照分析,经过统计学处理分析,认为对于腋部多汗症的患者,小剂量与大剂量的BTXA治疗方法的疗效间隔时间,差异有统计学意义.结论 大剂量A型肉毒毒素能够显著延长腋部多汗症复发间隔时间.     

A型肉毒毒素抑制病理性瘢痕形成机制的研究进展

A型肉毒毒素(botulinum toxin type A,BTXA)是一种神经调节剂,常用于医学美容领域.现已有大量研究显示,局部注射BTXA可安全有效地防治瘢痕,然而确切的分子机制仍不清楚.目前认为,BTXA可能通过降低伤口张力、调节miRNA水平、下调促纤维化因子表达、抑制成纤维细胞收缩、减少成纤维细胞数量和抑制...     

A型肉毒毒素局部注射治疗腋部臭汗症

目的:研究局部注射A型肉毒毒素治疗腋部臭汗症(腋臭)的机理、方法及疗效,探讨腋部臭汗症治疗新方法,为临床选择正确、合理的治疗方案提供重要的依据,避免手术的盲目性,减少并发症.方法:我科整形门诊腋臭就诊患者共计150人,随机分为两组:A型肉毒毒素注射组(BTXA注射组)和大汗腺清除术组(外科手术组).BTXA注射组,每侧腋部皮下注射生理盐水稀释的A型肉毒毒素50U,均匀注射,每个点注射约2～5U;外科手术组采用小切口皮下大汗腺清除术,术后1～3月随访患者,观察两组并发症,并建立两组等级资料,行秩和检验和x2检验,评价两组患者疗效差异.结果:两组疗效进行对照分析,经过统计学处理分析,认为对于轻、中度腋臭患者,两种治疗方法的疗效差异无显著性.结论:局部注射A型肉毒毒素治疗腋臭作为一种非手术治疗方法,为轻、中度腋臭患者提供了一种安全、快捷、有效的治疗选择.     

TNF-α McAb对急性失血性休克大鼠肝脏的作用

目的探讨肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)在急性失血性休克大鼠肝损伤中的作用及TNF-α单克隆抗体的保护作用。方法将24只雄性SD大鼠随机均分为三组:对照组(A组)、休克+乳酸林格氏液复苏组(B组)和休克+TNF-α单克隆抗体复苏组(C组)。B和C组大鼠通过股动脉放血,制作急性失血性休克动物模型;B组用乳酸林格氏液复苏,C组用含TNF-α单克隆抗体(3mg/kg)的乳酸林格氏液复苏,而A组在同等条件下不进行失血。分别检测各组大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、TNF-α水平和肝组织中MDA、SOD含量,并在光镜和电镜下观察各组大鼠肝组织的病理变化。结果 B、C组大鼠血清ALT、AST、TNF-α水平和肝组织中MDA含量较A组升高,SOD含量降低;C组ALT(343.63±35.61)U/L、AST(748.75±49.76)U/L、TNF-α(99.38±13.16)pg/mL、丙二醛(26.33±1.30)nmol/mgProt较B组ALT、AST、TNF-α、MDA含量降低,C组肝组织中SOD含量(510.14±47.44)U/mgProt较B组升高;在光镜、电镜下观察,C组肝组织损伤较B组减轻。结论 TNF-α可能是急性失血性休克肝损伤的重要因子之一,使用TNF-αMcAb复苏可以减轻失血性休克时大鼠肝损伤,具有一定的保护作用。     

Beneficial Effect of Pentoxifylline on Cisplatin-Induced Acute Renal Failure in Rabbits

Pentoxifylline (PTX) has been reported to inhibit TNF-α production and prevent several types of acute renal failure. This study was undertaken to determine the effect of PTX on the cisplatin-induced acute renal failure in rabbits. Rabbits received a single injection of cisplatin (5 mg/kg, i.p.) with or without PTX pretreatment (30 mg/kg, i.v.). Alterations in renal function, apoptotic cell death, and TNF-α mRNA expression were measured at 24 or 48 h after cisplatin injection. Cisplatin caused an increase in BUN and serum creatinine levels, a reduction in GFR, and an increase in fractional Na⁺ excretion. Such changes were significantly attenuated by PTX pretreatment (30 mg/kg, i.p.) 30 min before and 24 h after cisplatin injection. Morphological evaluation showed that cisplatin injection induced diffuse proximal tubular necrosis and the effect was reduced by PTX pretreatment. Cisplatin induced apoptotic cell death in renal cortex and the effect was significantly prevented by PTX. Treatment of opossum kidney cells with cisplatin resulted in cell death, which was significantly prevented by PTX. The increase in lipid peroxidation and the decrease in renal blood flow induced by cisplatin were not affected by PTX. The expression of TNF-α mRNA was increased after cisplatin injection and the effect was inhibited by PTX pretreatment. These results suggest that cisplatin-induced acute renal failure in rabbits is associated with an induction of TNF-α-mediated apoptosis, and that PTX may exert a protective effect against cisplatin nephrotoxicity by inhibiting TNF-α production.     

Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions

BACKGROUND: alpha-Melanocyte stimulating hormone (alpha-MSH) is an endogenous peptide that has remarkable anti-inflammatory and antimicrobial effects. These activities have been traced to the C-terminal tripeptide Lys-Pro-Val (KPV). A dimer composed of two KPV sequences connected with a Cys-Cys linker, (CKPV)2, is currently under clinical investigation for antimicrobial use. The present research was designed to evaluate effects of (CKPV)(2) on endotoxin-induced host reactions in vitro and in vivo. MATERIALS AND METHODS: Effects of (CKPV)2, KPV, and [Nle4-dPhe7]-alpha-MSH (NDP-alpha-MSH) on tumor necrosis factor alpha (TNF-alpha) production were determined: 1) in human peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) in vitro, and 2) in rats injected with LPS i.v. and sacrificed at 1 h. In additional experiments, dialysis peritonitis was induced in rats by adding LPS to dialysis fluid. Net ultrafiltrate was calculated and concentrations of nitrite (NO2-) and TNF-alpha were measured in blood and peritoneal fluid at 7 h. RESULTS: (CKPV)2 inhibited TNF-alpha production by LPS-stimulated human PBMC. This small peptide was as effective as NDP-alpha-MSH and more potent than KPV. Similar effectiveness was observed in vivo: 1 h after LPS injection, the large increase in circulating TNF-alpha was markedly reduced by (CKPV)2 treatment. In LPS-induced peritonitis, (CKPV)2 restored net ultrafiltrate to control values and significantly inhibited concentrations of TNF-alpha and NO2- both in plasma and in dialysate. CONCLUSIONS: The remarkable capacity of (CKPV)2 to inhibit endotoxin-induced host reactions suggests that it may be useful in treatment of inflammatory disorders.     

大鼠退变椎间盘中环氧化酶-2、缺氧诱导因子-1α的表达及其与血管生成的关系

目的探讨环氧化酶-2(COX-2)与缺氧诱导因子-1α(HIF-1α)在退变的大鼠椎间盘的表达相关性,以及它们与椎间盘内新生毛细血管生成的相关性。方法选取3个月龄的大白鼠20只,随机分为实验组与对照组。将实验组10只大鼠手术切除腰1-骶1棘突、关节突,棘上、棘间韧带,切断双侧竖棘肌,然后缝合切口。对照组不行手术。12周后,处死所有大鼠,立即取L4-5椎间盘。通过免疫组化方法检测两组实验动物椎间盘中COX-2、HIF-1α表达情况及微血管的密度(MVD)。并通过统计分析描述COX-2与HIF-1α之间的关系及它们分别与椎间盘微血管密度(MVD)之间的关系。结果实验组的髓核中HIF-1α、COX-2阳性细胞率明显增高,在对照组的髓核组织中极少出现阳性细胞。此外,实验组椎间盘中的微血管密度明显增加。用直线相关分析表明,实验组动物椎间盘髓核组织内HIF-1α、COX-2之间呈显著正相关关系(P<0.05,r=0.678)。经多元线性回归分析实验组椎间盘髓核组织中MVD值与HIF-1α的表达之间和MVD与COX-2的表达之间具有相关性(P均<0.05)。结论 1.大鼠椎间盘退变过程中HIF-1α、COX-2的表达有相互促进作用;2.退变椎间盘的MVD值与HIF-1α及COX-2的高表达具有相关关系。     

Interferon-α in combination with ribavirin as initial treatment for hepatitis C virus–associated cryoglobulinemic membranoproliferative glomerulonephritis

Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. In HCV-infected patients with MC, renal involvement worsens the overall prognosis because of a high incidence of infection or cardiovascular disease. The relationship between MC and HCV infection has prompted the use of antiviral therapy. Two patients with chronic HCV infection, type-II MC and membranoproliferative glomerulonephritis (MPGN), presenting as nephrotic syndrome were treated with interferon (IFN)-α (3 MU 3 times per week) and ribavirin (15 mg/kg daily) for 6 months. Laboratory tests included measurement of anti-HCV antibodies, HCV RNA, and HCV genotyping, and characterization of circulating cryoglobulins. A pretreatment renal biopsy was performed, and the histopathologic lesions were scored according to the index of disease activity. Viremia and cryoglobulinemia were suppressed in both patients. However, a complete remission of proteinuria was observed in 1 patient only. The evaluation of the renal biopsy specimens revealed a mild MPGN (activity score: 5/24) in the patient with remission of proteinuria and a severe MPGN (activity score: 15/24) in the patient who maintained a nephrotic-range proteinuria. Although a fully satisfactory treatment is not yet available, we feel that a reasonable therapeutic strategy for HCV-infected patients with MC nephritis could be as follows: (1) antiviral treatment alone for patients with a low-grade kidney involvement, and (2) a short-term course of steroids and cytotoxic drugs followed by antiviral therapy for acute exacerbations and/or rapidly progressive GN. © 2001 by the National Kidney Foundation, Inc.     

炎症标志物TNF-α、hs-CRP在肝癌患者预后评估中的作用

目的 探讨肝细胞癌（HCC）患者手术前后外周血肿瘤坏死因子-α（TNF-α）和高敏C-反应蛋白（hs-CRP）检测的临床意义。方法 检测201例HCC患者手术前后及70例健康对照者TNF-α和hs-CRP的水平,分析TNF-α和hs-CRP水平与临床病理特征的关系。结果 HCC患者术前TNF-α和hs-CRP水平显著高于健康对照者（P<0.05）,手术1周后TNF-α和hs-CRP水平较术前显著下降（P<0.05）。术前TNF-α和hs-CRP水平与HCC的Edmondson分级、TNM分期、肿瘤的大小、有无门静脉癌栓、有无肿瘤包膜密切相关（P<0.05）。hs-CRP水平还与有无腹水明显相关（P<0.05）。当确诊为HCC复发时,TNF-α和hs-CRP水平也明显高于术后水平（P均<0.01）。结论 术前TNF-α和hs-CRP水平与HCC临床病理特征有关,可作为HCC预后和复发的预测因子。