探讨四神丸、白头翁汤、连理汤对溃疡性结肠炎大鼠的影响  

Effect of Sishenwan,Baitouweng Tang,and Lianlitang on Ulcerative Colitis in Rats

作　　者：巩子汉 张玲[1] 刘丽梅[1] 卢贺起[1] 刘振丽[1] 柏冬[1] 王瑞海[1] 岳广欣[1] GONG Zi-han;ZHANG Ling;LIU Li-mei;LU He-qi;LIU Zhen-li;BAI Dong;WANG Rui-hai;YUE Guang-xin(Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中医基础理论研究所,北京100700

出　　处：《中国实验方剂学杂志》2021年第16期1-8,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中国中医科学院自主选题项目(Z02028)。

摘　　要：目的:探讨温方(四神丸)、清方(白头翁汤)、温清并用方(连理汤)治疗溃疡性结肠炎(UC)的作用机制,比较温、清、温清并用方对UC大鼠的作用差异。方法:将90只清洁级SD大鼠随机分为正常组和造模组,造模组采用2,4,6-三硝基苯磺酸(TNBS)灌肠法复制UC模型,将造模大鼠按随机数字表法分为模型组,阳性药组(柳氮磺吡啶,SASP),四神丸组,白头翁汤组和连理汤组,共5组。正常组和模型组大鼠给予2 mL·d^(-1)蒸馏水灌胃,四神丸、白头翁汤和连理汤组分别给予1.76,1.40及2.13 g·kg^(-1)·d^(-1)的对应中药灌胃,SASP组给予SASP 0.4 g·kg^(-1)·d^(-1)灌胃,各组给药量为2 mL·d^(-1),干预14 d。对各组大鼠结肠黏膜损伤程度评分及病理、细胞因子芯片进行检测,酶联免疫吸附测定法(ELISA)检测各组大鼠血浆游离甲状腺激素(FT3),胰高血糖素样肽-1(GLP-1),皮质酮(CORT)及结肠组织神经降压素(NT),P物质(SP),血管活性肠肽(VIP),生长抑素(SST)含量。结果:与正常组比较,UC大鼠结肠质量长度比及黏膜损伤评分显著升高(P<0.01);出现大量淋巴细胞浸润、肠绒毛紊乱甚至消失等现象;组织中性粒细胞趋化因子-1/2α/β/3(CINC-1/2α/β/3),白细胞介素-1α(IL-1α)及干扰素诱导蛋白10(IP-10)等因子含量显著升高(P<0.05);血浆CORT,GLP-1含量显著降低(P<0.05),组织SP含量显著升高(P<0.05);与模型组比较,各给药组大鼠结肠黏膜损伤减轻,连理汤、四神丸组大鼠IL-1α,IP-10,脂多糖诱导性C-X-C趋化因子(LIX),L选择素(L-selectin)等因子含量显著降低(P<0.05),白头翁汤组大鼠CINC-3,白细胞介素-17(IL-17)等因子含量显著降低(P<0.05),SASP组大鼠CINC-1/3,IL-1α,IP-10等因子含量显著降低(P<0.05);连理汤大鼠血浆FT3含量显著升高,连理汤、四神丸及白头翁汤大鼠血浆GLP-1含量显著升高(P<0.05);四神丸及白头翁汤大鼠结肠组织VIP含量显著降低(P<0.05),SASP大鼠结肠组织SST含量显著升高(P<0Objective: To explore the mechanism of Sishenwan,Baitouweng Tang,and Lianlitang in the treatment of ulcerative colitis(UC),and compare their efficacies on UC in rats. Method: Ninety SD rats of SPF grade were randomly divided into blank group(distilled water,2 mL·d^(-1))and experimental group. The rats in the experimental groups were administered with 2,4,6-trinitrobenzene sulfonic acid(TNBS)by clysis to induce the UC model. Subsequently, the model rats were divided into a model group(distilled water,2 mL·d^(-1)),positive group[sulfasalazine(SASP),0.4 g·kg^(-1)·d^(-1)],Sishenwan group(1.76 g·kg^(-1)·d^(-1)),a Baitouweng Tang group(1.40 g·kg^(-1)·d^(-1)),and Lianlitang group(2.13 g·kg^(-1)·d^(-1))according to the random number table. The rats in each group were dosed at 2 mL·d^(-1) for 14 days. The pathological score for colonic mucosa was detected. Cytokines were detected by the cytokine chip. The enzyme-linked immunosorbent assay(ELISA) was used to detect the free triiodothyronine(FT3), glucagon-like peptide-1(GLP-1), and corticosterone(CORT)in plasma,and neurotensin(NT),substance P(SP),vasoactive intestinal peptide(VIP),and somatostatin(SST)in colon tissues. Result: Compared with the normal group,the model group showed increased colon mass-length ratio and pathological score for colonic mucosa(P<0.01),infiltration of massive lymphocytes, disordered or absent intestinal villi, elevated levels of cytokine-induced neutrophil chemoattractant-1/2α/β/3(CINC-1/2α/β/3),interleukin-1α(IL-1α),interferon-inducible protein-10(IP-10)and other factors in colon tissues(P<0.05),dwindled CORT and GLP-1 levels in plasma(P<0.05),and increased SP content in colon tissues(P<0.05). Compared with the results in the model group,the mucosal injury in the colon of rats in each drug group was relieved. The levels of IL-1α,IP-10,lipopolysaccharideinducible CXC chemokine(LIX),and L-selectin of rats in the Lianlitang group and Sishenwan group were reduced(P<0.05),and the CINC-3 and IL-17 levels were diminished in the Baitou

关 键 词：四神丸 白头温汤 连理汤 溃疡性结肠炎 细胞因子芯片 大鼠 

分 类 号：R2-0[医药卫生—中医学] R22