The mechanism of Jiuyi powder and its effective components in inhibiting the M1 phenotype polarization of macrophages on chronic and refractory wounds infected by MRSA

Objective:To observe the effect of Jiuyi powder and its active components on the bacterial culture and macrophage phenotypic factors of the chronic refractory wound rat model,and to explore its mechanism of removing decay and promoting muscle growth.Methods:SD rats were divided into control group,Jiuyi powder group,Shengdan group,and calcined gypsum group,with 8 rats in each group.MRSA-infected skin lesions and wounds were used to build a model of chronic and difficult-to-heal wounds in rats.After the model was formed,the control group was treated with daily routine nitrofural disinfection and replaced with sterile gauze.On the basis of the control group,quantitative Jiuyi powder,Shengdan powder,and calcined gypsum powder were used for dressing change,once a day for 7 consecutive days.Before and after the last administration,collect rat wound secretions for bacterial culture,inducible monoxide nitrogen synthase content.At the same time,after the last administration,the rat wound tissue was excised for histopathology and immunofluorescence double staining to label macrophages and their M1 phenotype.Results:After the last dressing change,the wound healing of Jiuyi powder group was better than the other groups,and the wound healing rate of each group had significant difference(P<0.05).The histomology showed that the inflammation of Jiuyi powder group was controlled and had a healing trend.After the last drug change,the contents of TNF-α,IL-6 and iNOS in serum of all groups decreased,and the contents of IL-6,TNF-αand iNOS in serum of Jiuyi powder group decreased significantly before and after medication(P<0.05).There was statistical significance in serum IL-6 content between calcined gypsum group and Shengdan group before and after medication(P<0.05).In addition,the results showed that the contents of IL-6 and iNOS in serum of Jiuyi powder group were statistically different from those of the control group(P<0.05).Tissue immunofluorescence double staining showed that the positive rate of M1 macrophages in Jiuyi powder group and Shengdan group was significantly lower than that in control group(P<0.05).The MRSA negative conversion rate of Jiuyi powder group and Shengdan group was better than that of the control group and calcined gypsum group(P<0.05).Conclusion:Jiuyi powder can improve the inflammation of chronic refractory wounds,and has antibacterial,anti-corrosion and myogenic effects.Its mechanism may be related to the inhibition of macrophage M1 phenotype polarization.

九一丹及其有效组分抑制巨噬细胞M1表型极化对MRSA感染慢性难愈性疮面的作用机制

目的:观察九一丹及其有效组分对慢性难愈性疮面模型大鼠疮面细菌培养以及巨噬细胞表型因子的影响,分析其祛腐生肌的作用机制。方法:32只SD大鼠分成对照组、九一丹组、升丹组、煅石膏组,每组8只。采用MRSA感染皮损疮面造模法建立大鼠慢性难愈性疮面模型,成模后对照组予每日常规呋喃西林消毒更换无菌纱布处理,九一丹组、升丹组、煅石膏组在对照组基础上使用定量九一丹、升丹、煅石膏进行换药,每日1次,连续7 d。换药前及末次给药后采集大鼠疮面分泌物作细菌培养、分离血清检测肿瘤坏死因子-α(TNF-α)、诱导型一氧化氮合酶(iNOS)与白细胞介素(IL)-6对应的含量,同时在末次换药后,切除大鼠疮面组织用于组织病理检测和免疫荧光双染标记巨噬细胞M1表型。结果:末次换药后,九一丹组疮面愈合情况优于其余各组,各组疮面愈合率有显著性差异(P<0.05),组织形态学显示九一丹组炎症得到明显控制并具有愈合趋势;末次换药后,各组血清中TNF-α、IL-6、iNOS含量均呈下降趋势,九一丹组换药前后血清IL-6、TNF-α、iNOS含量下降明显(P均<0.05);煅石膏组与升丹组仅换药前后血清IL-6含量组内比较具有统计学意义(P均<0.05);另外,结果显示九一丹组换药后血清中IL-6、iNOS含量与对照组存在统计学差异(P均<0.05)。换药后组织免疫荧光双染结果提示,九一丹组、升丹组M1巨噬细胞阳性率明显低于对照组(P<0.05)。九一丹组及升丹组的MRSA转阴率优于对照组及煅石膏组(P<0.05)。结论:九一丹能够改善慢性难愈性疮面炎症情况,并有一定抑菌、祛腐、生肌的作用,而其潜在的作用机制可能与抑制疮面局部巨噬细胞M1表型极化有关。

九一丹外敷配合一期切开根治术治疗肛周脓肿临床疗效观察

目的:观察九一丹外敷对肛周脓肿术后创面的影响。方法:将40例肛周脓肿患者随机分为治疗组和对照组各20例,均采用一期切开根治术治疗,术后治疗组在前3天换药采用九一丹外敷,对照组换药采用常规三黄油纱条外敷。观察两组患者的治愈率、复发率、平均愈合时间、出现创缘水肿的例数。结果:经治疗后,两组患者治愈率和复发率比较无差异(P>0.05),两组创面愈合时间和创缘水肿例数比较有明显差异(P<0.05)。结论:在肛周脓肿术后早期换药时应用九一丹外敷,可以减少创缘水肿和促进创面愈合,值得临床推广应用。

偏最小二乘判别分析法在九一丹外用治疗浆细胞性乳腺炎中的安全性分析

目的应用偏最小二乘判别分析(partial least-squares discriminant analysis,PLSDA)法评估九一丹外用治疗浆细胞性乳腺炎的安全性及其临床价值。方法观察50例九一丹外用治疗浆细胞性乳腺炎患者在用药前、用药后第4天、停药第1、14天检测的血尿生化指标;在用药前、用药后第1、4、7天、停药第1、14天检测患者血汞、尿汞,并于停药第28天和停药3个月检测患者尿汞含量。并在用药前、用药后第1、4、7天及停药第1天记录创面情况,用药量及用药天数。在筛选到有重要影响的安全性指标后,PLSDA建立影响因素的潜在安全性判别模型,采用ROC曲线下面积评估模型的适用性,并使用变量重要性投影(variable importance in the projection,VIP)评价潜在的重要影响因素。结果九一丹外用治疗浆细胞性乳腺炎对尿β2-微球蛋白(β2-MG)、尿N-乙酰-β氨基葡萄糖苷酶(NAG)、24 h尿蛋白及α1微球蛋白(α1-MG)影响较大;PLSDA判别模型预测准确率为74.00%,模型的特异度、灵敏度及ROC曲线下面积分别为0.7826、0.7037及0.8084。通过模型筛选到3个对潜在安全性具有较大影响的因素:用药前疮腔体积、用药天数和用药量。结论PLSDA法能够用于分析中医临床的相关信息,筛选出九一丹外用安全性监测的主要指标为尿β2-MG和尿NAG;用药量和用药时间是影响血汞、尿汞的最主要因素,依据这两大因素建立的九一丹治疗浆细胞性乳腺炎安全性分级仿真模型能在一定程度上评估临床九一丹外用的安全性。