双藤痹痛凝胶对CIA大鼠外周血调节性T细胞的作用研究

目的:分析双藤痹痛凝胶对胶原免疫性关节炎大鼠外周CD_(4)~+CD_(25)~+FoxP3~+Treg细胞的调节作用。方法:Wistar大鼠50只,随机分成5组,分别为正常组、模型组、双藤痹痛凝胶高剂量组、中剂量组、低剂量组,胶原蛋白诱导大鼠关节炎,并采用流式细胞术检测大鼠外周血CD_(4)~+CD_(25)~+FoxP3~+Treg及酶联免疫吸附试验检测血清中IL-6表达水平。结果:与模型组比较,双藤痹痛凝胶高、低剂量组大鼠外周血CD_(4)~+CD_(25)~+T细胞及CD_(4)~+CD_(25)~+FoxP3~+Treg细胞水平显著升高,且高、中剂量组血清IL-6水平显著下降。结论:双藤痹痛凝胶治疗类风湿性关节炎可能通过上调外周血CD_(4)~+CD_(25)~+FoxP3~+Treg细胞表达水平,降低血清IL-6水平,从而恢复免疫耐受作用。     

全蝎-蜈蚣对CIA大鼠外周血协同刺激分子B7-1,B7-2表达的影响

目的:观察全蝎-蜈蚣对胶原免疫性关节炎( collagen-induced arthritis,CIA)大鼠外周血协同刺激分子B7-1(CD80)、B7-2(CD86)表达的影响.方法:Wistar大白鼠60只,随机分成6组,即正常组,模型组,全蝎-蜈蚣高,中,低剂量组,Ⅱ型胶原蛋白( typeⅡcollagen,CⅡ)组.采用Ⅱ型胶原蛋白诱导法复制大鼠关节炎模型,并ig给予全蝎-蜈蚣混悬液(0.4,0.2,0.1 g·kg-1)进行干预,CⅡ组予CⅡ白冻干粉60 μg· kg -1 ig进行对照,共计40 d.并采用流式细胞术检测大鼠外周血单核细胞表达CD80,CD86情况.结果:与正常组大鼠外周血 CD80+(44.8±11.61)％ CD80+CD86-(32.4±9.18)％比较,模型组大鼠外周血CD80+细胞(55.7±6.31)％及CD80+ CD86 -细胞(43.7±10.26)％水平显著升高(P＜0.05);与模型组比较,全蝎-蜈蚣中、低剂量组大鼠外周血CD80+细胞(46.6±6.34)％,(30.8±15.14)％明显降低(P＜0.05),及且全蝎-蜈蚣低剂量组大鼠外周血CD80+ CD86 -细胞(25.3±12.67)％水平显著下降(P＜0.05).结论:全蝎-蜈蚣药对治疗CIA大鼠的作用机制可能与降低外周血单核细胞表达CD80+及CD80+ CD86 -分子表达水平相关.     

全蝎蜈蚣对CIA大鼠外周血和小肠黏膜 T细胞亚群的影响

目的:观察全蝎蜈蚣对CIA大鼠外周血和小肠黏膜T细胞亚群的影响.方法:60只Wistar大鼠除正常组外均复制胶原免疫性关节炎后,并随机分成模型组、全蝎蜈蚣高、中、低剂量组和Ⅱ型胶原蛋白治疗组,给药40d,采用流式细胞术检测大鼠外周血和小肠黏膜T细胞亚群水平.结果:与正常组比较,模型组大鼠外周血和PP结T淋巴细胞均表现为CD4*T细胞明显升高或有升高趋势,CD4+/CD8+则在外周血升高而在PP结下降(P＜0.05或P＜0.01).与模型组比较,所有治疗组对CD3+T淋巴细胞作用不明显,全蝎蜈蚣各剂量组均可明显下调PP结CD4+,CD8+T细胞水平,升高CD4+/CD8+水平(P＜0.05或P＜0.01),同时外周血方面高、中剂量组CD4+T淋巴细胞水平及CD4+/CD8+显著下降(P＜0.05或P＜0.01),但对CD8+T淋巴细胞作用不明显.结论:全蝎蜈蚣治疗类风湿性关节炎的可能途径是调节CIA大鼠外周血和肠黏膜局部T淋巴细胞平衡.     

梅毒血清固定患者外周血CD4~+CD25~+ Treg和CD4~+CD25~+Foxp3~+ Treg的表达及意义

目的检测并比较梅毒血清固定患者与治疗后快速血浆反应素环状卡生试验(RPR)转阴患者外周血CD4+CD25+Treg以及CD4+CD25+Foxp3+Treg的表达情况。方法运用流式细胞术检测40例梅毒血清固定患者(实验组)和40例治疗后RPR转阴的梅毒患者(对照组)外周血CD4+CD25+Treg和CD4+CD25+Foxp3+Treg的表达水平并进行比较。结果实验组患者外周血CD4+CD25+Treg细胞占外周血CD4+T细胞总数的(11.90±0.64)%,对照组为(9.09±0.28)%,2组比较差异有统计学意义(t=4.01,P0.001);实验组CD4+CD25+Foxp3+Treg细胞占外周血CD4+T细胞总数的(6.25±0.28)%,对照组为(3.37±0.24)%,2组比较差异有统计学意义(t=7.90,P0.001)。结论血清固定梅毒患者外周血中抑制性CD4+CD25+Treg细胞的比例明显高于RPR转阴梅毒患者,且其中大部分为具有抑制活性的CD4+CD25+Foxp3+Treg细胞亚群,推测这类Treg细胞在CD4+T细胞中所占的比例增加与梅毒患者血清固定有一定关系。     

安胎汤对先兆流产大鼠CD4~+ CD25~+ Foxp3~+ Treg细胞免疫调节的影响

目的:从CD4~+ CD25~+ Foxp3~+ Treg细胞变化角度探讨安胎汤对先兆流产大鼠的影响及作用机制。方法:将大鼠雌雄以2∶1的比例配对后筛选出孕鼠48只,以缩宫素及针灸合谷、三阴交穴的方法建立先兆流产模型,随机分为6组,分别为正常妊娠组、安胎汤低剂量组、安胎汤中剂量组、安胎汤高剂量组、黄体酮组及先兆流产大鼠模型组。于妊娠第13天取大鼠外周血后即用流式细胞仪检测CD4~+ CD25~+ Foxp3~+ Treg细胞百分率,然后处死大鼠,计数双侧子宫着床点数及活胎数。结果:安胎汤可提高先兆流产孕鼠胚胎吸收率和CD4~+ CD25~+ Foxp3~+ Treg细胞百分率,降低胚胎吸收率(P0.01)。结论:安胎汤通过调节先兆流产大鼠CD4~+ CD25~+ Foxp3~+ Treg细胞百分率达到保胎目的,且疗效与剂量相关。     

全蝎蜈蚣对胶原免疫性关节炎大鼠的关节损伤改善作用

目的:观察全蝎蜈蚣对胶原免疫性关节炎大鼠的病理损伤改善作用。方法:大鼠随机分成6组:正常对照组、模型对照组、全蝎蜈蚣高、中、低剂量组和Ⅱ型胶原蛋白治疗组(CⅡ组),全蝎蜈蚣高中低剂量组分别给予全蝎蜈蚣混悬液0.4g/kg、0.2g/kg、0.1g/kg灌胃、CⅡ组予Ⅱ型胶原蛋白冻干粉60μg/kg灌胃;正常对照组和模型对照组分别用等容积生理盐水灌胃,连续给药40d。采用Ⅱ胶原蛋白诱导大鼠关节炎,同时就大鼠体重、关节疼痛评分、病理损伤评分及病理形态学改变进行观察。结果:在第三周后全蝎蜈蚣高中剂量(0.4g/kg、0.2g/kg)组大鼠体重明显高于模型组(P<0.01或P<0.05),第15天以后各剂量组(0.4g/kg、0.2g/kg、0.1g/kg)即可缓解CIA大鼠的关节疼痛,其疼痛评分明显低于模型组(P<0.01或P<0.05),且治疗组病理形态学可见关节软骨破坏程度减轻,少量炎细胞浸润,滑膜细胞增生,伴有纤维结缔组织增生,其病理损伤评分也明显低于模型组(P<0.01或P<0.05)。结论:全蝎蜈蚣药对可有效抑制CIA大鼠关节疼痛,促进体重增长和病理性损伤修复。     

薏苡仁酯对胶原诱导性关节炎小鼠Foxp3+CD4+CD25+调节性 T 细胞影响的研究

目的研究薏苡仁酯对胶原诱导性关节炎(collagen induced arthritis,CIA)小鼠外周血中Foxp3+CD4+CD25+调节性T细胞(Treg)的影响,探讨薏苡仁酯类风湿关节炎治疗中的可能机制。方法从25只小鼠随机选取5只为正常组,剩余20只小鼠进行CIA造模。造模成功后随机分为造模对照组10只及薏苡仁酯组10只。薏苡仁酯组予薏苡仁酯注射液25 m L/kg,正常组及造模对照组注射生理盐水25 m L/kg,均每天腹腔内注射1次。共用药21天。用药后对各组关节炎进行评分,计算关节炎指数,并应用流式细胞术测定小鼠外周血Foxp3+CD4+CD25+Treg比例。结果与正常组比较,造模对照组关节炎指数明显升高(P0.01),薏苡仁酯组较造模对照组小鼠关节炎指数明显下降(P0.01)。与正常组比较,造模对照组Foxp3+CD4+CD25+Treg水平均明显下降(P0.01),薏苡仁酯组较造模对照组用药后Foxp3+CD4+CD25+Treg水平明显升高,差异有统计学意义(P0.01)。结论薏苡仁酯能上调CIA小鼠Foxp3+CD4+CD25+Treg比例,可能在CIA的发病中具有一定的免疫调节作用。     

薏苡仁酯对胶原诱导性关节炎小鼠Foxp3^+ CD4^+ CD25^+调节性T细胞影响的研究北大核心CSCD

目的研究薏苡仁酯对胶原诱导性关节炎(collagen induced arthritis,CIA)小鼠外周血中Foxp3+CD4+CD25+调节性T细胞(Treg)的影响,探讨薏苡仁酯类风湿关节炎治疗中的可能机制。方法从25只小鼠随机选取5只为正常组,剩余20只小鼠进行CIA造模。造模成功后随机分为造模对照组10只及薏苡仁酯组10只。薏苡仁酯组予薏苡仁酯注射液25 m L/kg,正常组及造模对照组注射生理盐水25 m L/kg,均每天腹腔内注射1次。共用药21天。用药后对各组关节炎进行评分,计算关节炎指数,并应用流式细胞术测定小鼠外周血Foxp3+CD4+CD25+Treg比例。结果与正常组比较,造模对照组关节炎指数明显升高(P<0.01),薏苡仁酯组较造模对照组小鼠关节炎指数明显下降(P<0.01)。与正常组比较,造模对照组Foxp3+CD4+CD25+Treg水平均明显下降(P<0.01),薏苡仁酯组较造模对照组用药后Foxp3+CD4+CD25+Treg水平明显升高,差异有统计学意义(P<0.01)。结论薏苡仁酯能上调CIA小鼠Foxp3+CD4+CD25+Treg比例,可能在CIA的发病中具有一定的免疫调节作用。     

补肾生血法对慢性再生障碍性贫血患者CD4~+CD25~+Treg的影响

目的:探讨补肾生血法对慢性再生障碍性贫血(CAA)患者外周血CD4+CD25+Treg的影响,进一步阐述补肾生血法治疗CAA的疗效机制。方法:应用流式细胞术检测CAA患者治疗前后外周血CD4+CD25+Treg的表达水平。结果 :治疗组治疗前患者外周血CD4+CD25+Treg水平低于正常对照组(P0.05),治疗后外周血CD4+CD25+Treg水平较治疗前明显升高(P0.05);治疗组治疗后与正常对照组比较,无显著性差异(P0.05)。结论:补肾生血法通过提高CAA患者外周血CD4+CD25+Treg的表达水平,抑制异常的细胞免疫状态,以促进骨髓造血功能的恢复。     

安子合剂对ACA阳性先兆流产患者CD4~+CD25~+FOXP3~+Treg细胞免疫调节的影响

目的:观察安子合剂对ACA阳性先兆流产患者CD4+CD25+FOXP3+Treg细胞免疫调节的影响。方法:选取ACA阳性先兆流产患者为治疗组(27例),给服中药安子合剂,125ml,2次/日,连服4周;选取正常孕妇为对照组(15例)。检测患者治疗前后及正常孕妇外周血CD4+CD25+FOXP3+Treg细胞的比例,并测定患者治疗前后血清ACA指标、B超检查胚胎发育情况等。结果:治疗组患者治疗前CD4+CD25+FOXP3+Treg细胞的比例显著低于正常妊娠对照组(P<0.01);治疗后,其细胞比例显著高于治疗前(P<0.01)。27例患者中20例ACA阳性的转阴率达85.00%,7例ACA定量滴度较治疗前显著下降(P<0.01)。保胎的成功率达92.59%。结论:ACA阳性先兆流产患者外周血CD4+CD25+FOXP3+Treg细胞的比例低于正常妊娠妇女,存在免疫调节异常;安子合剂治疗ACA阳性先兆流产的作用机理之一与增加CD4+CD25+FOXP3+Treg细胞的比例、调节妊娠期机体免疫功能有关。     

异基因脐血干细胞穴位移植对类风湿关节炎大鼠外周血CD_4~+CD_(25)~+调节性T细胞的影响

目的:观察异基因脐血干细胞(h UCBSCs)穴位移植对类风湿关节炎大鼠外周血CD4+CD25+调节性T细胞(CD4+CD25+Treg)的干预作用及相关机制。方法:先进行脐血CD34+细胞分选,将100只大鼠随机分为正常对照组、模型组对照组、h UCBSC尾静脉注射治疗组、h UCBSCs外关穴注射治疗组、甲氨喋呤(MTX)灌胃治疗组,每组20只。采用邓安梅法建立胶原诱导性关节炎(CIA)大鼠模型。于大鼠免疫后第31天(除正常组及模型组用等体积蒸馏水)向外关穴、尾静脉注射0.5 m L氯化钠注射液和0.5m L h UCBSCs悬液(含干细胞2×107/m L),4周后采用流式细胞仪,对外周血CD4+CD25+细胞的百分含量及其在CD4+T淋巴细胞中所占的比例进行检测。结果:h UCBSCs外关穴注射治疗组外周血CD4+CD25+细胞的百分含量及其在CD4+T淋巴细胞中所占的比例与甲氨喋呤组比较明显增高,差异有统计学意义(P<0.01),h UCBSC尾静脉注射治疗组与甲氨喋呤组比较,无显著性差异(P>0.05)。结论:h UCBSCs外关穴穴位注射治疗可能通过上调CD4+CD25+调节性T细胞水平,抑制关节炎症和关节骨破坏吸收,有助于类风湿关节炎的治疗。     

苏木、苏木+黄芪对荷瘤小鼠CD4~+ CD25~+调节性T细胞及相关调控分子的干预作用

目的:观察苏木、苏木+黄芪对荷瘤小鼠脾CD4+CD25+调节性T细胞(Treg)表达及相关调控分子的干预作用。方法:复制C57BL/6小鼠Lewis肺癌动物模型,动态观察苏木、苏木+黄芪抑瘤率、肺转移抑制率,流式细胞术检测小鼠脾CD4+CD25+Treg表达,免疫磁珠分选小鼠脾CD4+CD25+细胞,RT-PCR检测小鼠脾CD4+CD25+细胞和瘤组织Foxp3、CTLA-4mRNA表达。结果:苏木组6d、苏木+黄芪组10d瘤重低于荷瘤对照组(P0.05);苏木+黄芪组20d肺转移抑制率为77.75%;15d苏木+黄芪组小鼠脾CD4+CD25+细胞表达低于荷瘤对照组(P0.05);苏木+黄芪组荷瘤小鼠瘤组织CTLA-4、Foxp3mRNA表达及脾CD4+CD25+分选后细胞Foxp3 mRNA表达低于荷瘤对照组(P0.05)。结论:益气活血中药组方苏木+黄芪可调节荷瘤小鼠脾Treg及相关调控分子表达,并且在淋巴组织和肿瘤微环境中都表现出作用。     

Beneficial therapeutic effect of Chinese herbal Bushen formula on CHB patients with mildly elevated alanine aminotransferase by down-regulating CD4+CD25+T cells

Ethnopharmacological relevance

To investigate the clinical effects of the Bushen formula on chronic hepatitis B (CHB) patients with mildly elevated alanine aminotransferase (ALT) (1–2 times ULN) and its relevant immune mechanism.

Materials and methods

Fifty CHB patients were enrolled, and they were categorized into two groups according to infection state, including CHB carrier group(24 patients) and mildly elevated ALT (1–2 times ULN) group (26 patients), and 12 healthy volunteers were collected as normal control group. In addition, patients with mildly elevated ALT were taking the Bushen formula for 6 months. Biochemical assessment, viral load quantitation and HBV markers were examined at the Department of Clinical Laboratory, Shanghai Shuguang Hospital. Peripheral blood mononuclear cells were separated from patients and healthy volunteers. T cells were separated from healthy blood, and Hepatitis B core antigen (HBcAg) was added to the culture media. The percentage of CD4+CD25+T cells and the expression levels of IFN-γ and IL-4 were examined by flow cytometry and the expression level of FoxP3 was examined by real-time PCR and flow cytometry. The Chinese medicine symptom complex score was calculated.

Results

The percentage of CD4+CD25+T cells and the expression level of Foxp3 in two CHB patient groups were higher than that in the normal control group, and the percentage of CD4+CD25+T cells and the expression level of Foxp3 in the CHB carrier group were highest. The experiment in vitro showed that both the percentage of CD4+CD25+T cells and the expression of Foxp3 were elevated by HBcAg in CD4+T cells separated from normal peripheral blood. In patients with mildly elevated ALT, the serum ALT level was significantly decreased from 81.77±18.24 U/L to 64.92±20.60 U/L and the serum HBV DNA level was significantly decreased from 6.54±0.95 (log) to 5.15±2.22 (log), and symptom scores were significantly decreased from 6.19±3.99 to 2.77±1.66 after administration of the Bushen formula. In addition, we found that the frequency of CD4+CD25+T cells correlated negatively with the expression level of IFN-γ in CD4+T cells from CHB patients with mildly elevated ALT, and the percentage of CD4+CD25+T cells was decreased from 11.07±4.30% to 8.70±3.49% and the expression level of IFN-γ in CD4+T cells was increased from 13.98±3.25% to 15.85±3.43% after administration of the Bushen formula.

Conclusion

In CHB patients, the percentage of CD4+CD25+T cells and the expression of Foxp3 in peripheral blood were increased, which can be repeated in HBcAg-stimulated healthy CD4+T cells. The Bushen formula has positive effects on CHB patients with mildly elevated ALT (1–2 times ULN) by reducing serum ALT and HBV DNA levels, which is relevant with the decreasing of the percentage of CD4+CD25+T cells and the increasing of the expression level of IFN-γ in CD4+T cells.     

加味升降散对饮停胸胁型结核性胸膜炎患者胸腔积液ADA,外周血Treg细胞及DC细胞亚群的影响

目的:探讨饮停胸胁型结核性胸膜炎(TBP)患者应用加味升降散对其胸腔积液腺苷脱氨酶(ADA)及外周血调节性T细胞(Treg)与树突状细胞(DC)细胞亚群的影响。方法:选取河北大学附属医院2014年1月—2015年9月收治的134例TBP患者,按照随机数字表法均分为两组。对照组予以胸腔穿刺抽液+抗结核药物的常规治疗;观察组在此基础上,给予加味升降散治疗。记录比较两组连续治疗2个月时临床疗效,胸腔积液ADA水平,外周血Treg与DC细胞亚群占外周血单个核细胞(PBMC)的百分比。结果:连续治疗2个月后,观察组总有效率(95.52%)高于对照组(83.58%)(P0.05)。两组治疗2个月时胸腔积液ADA水平均显著低于治疗前(P0.01);与对照组同期比较,观察组治疗2个月时胸腔积液ADA水平显著降低(P0.01)。与治疗前比较,两组患者治疗2个月时CD25~+/PBMC,CD25~+/CD4~+及CD25~+FoxP3~+/CD25~+均显著降低(P0.01);且观察组治疗2个月时外周血Treg细胞亚群改善程度较对照组同期降低显著(P0.01)。两组治疗2个月时DC1/PBMC,DC2/PBMC及DC1/DC2均明显高于治疗前(P0.05);且与对照组同期比较,观察组治疗2个月时外周血DC细胞亚群改善幅度更为明显(P0.05)。结论:TBP患者在常规西医治疗基础上应用加味升降散更能有效改善其临床症状,降低胸腔积液ADA水平,调节机体细胞免疫,疗效切实,为临床防治TBP提供了新思路。     

Effects of Yishenjiangzhuo granules on immunity and bone metabolism in patients with stage 3-4 chronic kidney disease

Objective

To determine the effects of Yishenjiangzhuo granules (YJG) on bone metabolism and to explore the changes in levels of bone Gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), as well as their relationships with levels of B cells, regulatory T cells (Treg) and interleukin (IL)-17 in patients with stage 3-4 chronic kidney disease (CKD) before and after treatment.

Methods

Fifty-three stage 3-4 CKD patients were divided randomly into two groups: YJG treatment and control. Peripheral blood was taken from two groups of CKD patients and 21 healthy subjects in the normal group. The parameters determined were the levels of CD4 +, CD19 +, CD19 + CD69 +, CD19 + AV, Treg (CD4 + CD25 + CD127^l°), BGP, TRAP, IL-17, calcium, phosphate, blood urea nitrogen, serum creatinine (SCr), hemoglobin (Hb) in peripheral blood, and urinary creatinine. Calcium-phosphate products and endogenous creatinine clearance rate (CCr) were calculated according to standard protocols.

Results

In YJG and control groups, SCr levels were lowered (P<0.01) after treatment, whereas CCr (P<0.05) as well as Hb and albumin levels (P< 0.01) were increased. The changes in levels of CCr and SCr in the YJG group were more significant. After treatment, CD19+CD69+ and Treg levels in the two groups varied (P<0.01) compared with those of the normal group; the level of CD19+ increased but the levels of CD4 + and CD19 + AV decreased (P< 0.01) in both groups. Compared with the control group, the changes of CD19+ and CD19+AV in the YJG group were more apparent (P<0.05). Compared with the normal group, levels of IL-17 in both groups increased significantly (P<0.01), and the difference in the control group was more significant (P<0.05). After treatment, the TRAP level increased (P<0.05), but the difference in BGP level (P>0.05) was not significant.

Conclusion

In stage 3-4 CKD patients, B cells and IL-17 participated in the induction of osteoclast activation. YJG could also elevate the level of B cells and decrease their apoptosis, but showed no significant effects on active B cells, IL-17 or osteoclast activity.     

双氢青蒿素对AA大鼠外周血T淋巴细胞的调节作用

目的:探讨双氢青蒿素对佐剂性关节炎(AA)大鼠外周血T细胞的调节作用.方法:采用佐剂性关节炎动物模型,将体重160～ 180 g的SD大鼠随机设为6组:正常对照组、模型对照组、甲氨蝶呤对照组(1mg·kg-1)、双氢青蒿素高、中、低剂量(11.2,5.6,2.8 mg·kg-1)组,造模2周后灌胃给药,连续给药28 d,并采用流式细胞术检测外周血T淋巴细胞亚群、酶联免疫法检测血清白介素-4 (IL-4)、干扰素-γ(IFN-γ)的水平.结果:相较于正常组,模型组外周血CD4+T,CD4+ T/ CD8+T和血清IFN-γ水平显著升高(P＜0.01),血清IL-4水平显著降低(P＜0.01),CD3+T,CD8+T则无明显变化;高、中剂量双氢青蒿素组CD4+T所占百分比分别是(34.81±3.80)％,(34.92±5.14)％,CD4+ T/ CD8+T分别是2.21±0.43,2.27±0.48,与模型组相比显著降低(P＜0.05,P＜0.01);双氢青蒿素高、中、低剂量组血清INF-γ水平分别是(15.90±2.05),(16.27 ±2.11),( 18.15±2.15) ng·L-1,与模型组相比显著降低(P＜0.01);IL-4水平分别是(40.21±4.89),(40.04±4.56),(34.81±4.02)ng·L-1,与模型组相比显著升高(P＜0.01),其调节作用在2.8 ～5.6 mg·kg-1范围呈剂量依赖性(P＜0.05).结论:双氢青蒿素能有效改善AA大鼠T细胞功能紊乱状况,为其应用于类风湿关节炎治疗奠定实验基础.     

补肾益肺解毒法对Lewis肺癌小鼠CD4~+CD25~+调节性T细胞、Foxp3及B7-H3的影响

目的:研究补肾益肺解毒法对Lewis肺癌小鼠CD4~+CD25~+调节性T细胞(T regulatory cell,Treg)、转录因子Foxp3及共刺激因子B7-H3表达的影响。方法:建立32只6~8周龄C57BL/6雄性小鼠Lewis肺癌细胞皮下移植瘤模型后,将32只造模后小鼠随机分为模型组、中药组、化疗组及综合组,每组各8只,单笼饲养。模型组以0.4 m L生理盐水灌胃14 d,并分别在第1天、第3天、第5天腹腔注射生理盐水1 m L;中药组以0.4 m L中药液灌胃14 d,并分别在第1天、第3天、第5天腹腔注射生理盐水1 m L;化疗组以0.4 m L生理盐水灌胃14 d,分别在第1天、第3天、第5天腹腔注射DDP溶液1 m L;综合组以0.4 m L中药液灌胃14 d,在第1天、第3天、第5天腹腔注射DDP溶液1 m L。给予药物干预14d后,观察小鼠的一般状况、饲料消耗量、体质量、去瘤体质量、移植瘤质量等,流式细胞术检测各组小鼠外周血和移植瘤CD4~+CD25~+Treg细胞的比例、Foxp3以及B7-H3的含量。结果:补肾益肺解毒法可改善肺癌小鼠的行为体征,增加饲料消耗量、体质量和去瘤体质量,减少移植瘤重量,与模型组比较,差异有统计学意义(P0.05)。补肾益肺解毒法治疗可显著降低Lewis肺癌小鼠外周血和移植瘤CD4~+CD25~+Treg细胞、Foxp3以及B7-H3的水平,与模型组比较差异有统计学意义(P0.05)。结论:补肾益肺解毒法通过降低CD4~+CD25~+Treg细胞、Foxp3以及B7-H3的水平增强机体的抗肿瘤免疫应答发挥抑瘤作用。     

新风胶囊对佐剂关节炎大鼠肺功能及Notch信号传导通路的影响

目的：观察新风胶囊对佐剂关节炎（AA）大鼠足跖肿胀度（E）、关节炎指数（AI）、肺系数（LI）、肺功能变化、调节性T细胞（Treg）及肺组织Notch受体、配体表达的影响。方法：将84只大鼠随机分为正常对照（NC）组、模型（Model）组、甲氨喋呤(MTX)组、雷公藤多苷片（TGT）组和新风胶囊低剂量（XFC-L）组、新风胶囊中剂量（XFC-M）组、新风胶囊高剂量（XFC-H）组,每组12只,分别给动物右后足跖皮内注射弗氏完全佐剂（FCA）0.1mL致炎（除NC组外）,致炎后第19d开始给药。NC组及Model组均给予生理盐水,其余5组分别给予MTX、TGT、XFC。观察各组大鼠上述各指标的变化。结果：①与NC组相比,Model组大鼠E、AI、LI在1s内平均呼气流量（FEV1/FVC）、肺泡炎积分、Notch3、Notch4、Delta1表达明显升高（P<0.01）;用力肺活量（FVC）、25%肺活量的最大呼气流量（FEF25）、50%肺活量的最大呼气流量（FEF50）、75%肺活量的最大呼气流量（FEF75）、最大呼气中期流量（MMF）、用力最大呼气流量（PEF）、CD4+ T细胞、CD25+ T细胞、CD4+ CD25+ Treg、Notch1、Jagged1、Jagged2表达明显降低（P<0.01）。②与Model组相比,各治疗组大鼠体重、FVC、FEF25、FEF50、FEF75、MMF、PEF、Notch1、Jagged1、Jagged2及Treg的表达升高;E、AI、LI、FEV/FVC及Notch3、Notch4、Delta1的表达降低（P<0.05或P<0.01）。③与XFC-M组相比,其余各治疗组LI、肺泡炎积分及Notch3、Delta1升高;FVC、FEF25、FEF50、FEF75、MMF、PEF及Notch1、Jagged1、CD4+ T细胞、CD4+ CD25+ Treg降低（P<0.05或P<0.01）。结论：AA大鼠存在关节局部的炎症反应和肺功能的降低,通过相关分析得知肺功能降低与Notch信号传导通路的表达有关;新风胶囊能明显改善AA大鼠关节症状和肺功能,可能通过促进Delta1、Notch3、Notch4的表达、抑制Jagged1、Jagged2、Notch1表达,降低炎症反应和免疫复合物沉积,改善关节和肺部症状。