益胃消瘀颗粒对胃黏膜肠化大鼠及相关炎症介质的影响
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摘要
目的观察益胃消瘀颗粒(YWXY)对胃黏膜肠化大鼠血液及胃组织炎症相关介质的影响,并分析其治疗胃黏膜肠化的可能机制。方法选8周雄性SD大鼠60只,按随机数字表分为空白组、模型组、YWXY高剂量组、YWXY中剂量组、YWXY低剂量组、胃复春(WFC)组6组,每组10只。采用N-甲基-N'-硝基-N-亚硝基胍(MNNG)造模,6个月及7个月后分次抽检3只,造模成功后进入给药阶段,给药3个月后观察大鼠胃组织学改变,ELISA法检测大鼠血清及胃黏膜肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-1β)、胃泌素(GAS)、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,RT-q PCR检测胃黏膜标本中核转录因子-κB(NF-κB)的表达。结果光镜下模型组可见黏膜萎缩及肠化,而YWXY高、中剂量组萎缩及肠化均较模型组明显改善,低剂量组及胃复春组萎缩及肠化较模型组有所减轻。模型组胃黏膜NF-κB表达均较空白组升高(P <0. 01),模型组血清及胃黏膜TNF-α含量均较空白组升高(P <0. 01);与模型组比较,YWXY高、中剂量组血清TNF-α含量降低(P <0. 01)。模型组血清及胃组织IL-1β含量较空白组升高(P <0. 01);与模型组比较,YWXY高、中、低剂量组血清及胃黏膜IL-1β含量降低(P <0. 01、P <0. 05)。模型组血清及胃黏膜SOD1、SOD2与MDA含量与空白组比较差异有统计学意义(P <0. 01);与模型组比较,YWXY高、中、低剂量组血清及胃黏膜SOD1、SOD2含量均升高(P <0. 01,P <0. 05),YWXY高、中剂量组血清SOD2升高(P <0. 01)。与空白组比较,模型组血清及胃黏膜MDA含量均升高(P <0. 01);与模型组比较,YWXY高、中、低剂量组血清及胃黏膜MDA含量降低(P <0. 01,P <0. 05)。结论YWXY能够改善萎缩性胃炎大鼠的肠上皮化生,其机制可能与抑制NF-k B表达,降低TNF-α、IL-1β、MDA含量水平,升高GAS、SOD1、SOD2含量水平有关。
Objective To observe the effects of yiwei xiaoyu granules( YWXY) on intestinal metaplasia of gastric mucosa and the related inflammatory mediators of the gastric tissue in the rats and analyze the potential mechanism of this drug in the treatment of intestinal metaplasia of gastric mucosa. Methods A total of 60 female SD rats,8 weeks in age were collected and divided into a blank group,a model group,a high-dose YWXY group,a middle-dose YWXY group,a low-dose YWXY group and a weifucun( WFC) group,10 rats in each one according to the random number table. N-methyl-N'-nitro-N-nitroso guanidine was adopted for modeling. Separately,in 6 and 7 months,3 rats were randomly checked. After modeling success,the drug intervention started. After medication for 3 months,the histological changes of the gastric tissue were observed. ELISA method was used to determine the levels of TNF-α,IL-1β,GAS,SOD and MDA. RT-q PCR was adopted to determine the expression of NF-κB in the sample of gastric mucosa. Results Under microscope,the mucosal atrophy and intestinal metaplasia were visible in the model group. The mucosal atrophy and intestinal metaplasia were relieved obviously in the high-dose and middle-dose YWXY groups as compared with the model group. The mucosal atrophy and intestinal metaplasia were reduced in the low-dose group and WFC group as compared with the model group. NF-κB expression in the gastric mucosa in the model group was increased as compared with theblank group( P < 0. 01). The levels of TNF-α in serum and gastric mucosa in the model group were all increased as compared with the blank group( P < 0. 01). Compared with the model group,the levels of TNF-α in serum were reduced in the high-dose and middle dose YWXY group( P < 0. 01). The levels of IL-1β of the serum and the gastric issue in the model group were increased as compared with the blank group( P < 0. 01). Compared with the model group,the levels of IL-1β of the serum and the gastric issue were reduced in the high-dose,middle-dose and low-dose YWXY groups( P <0. 01,P < 0. 05). The differences in SOD1,SOD2 and MDA of the serum and the gastric issue were significant between the model group and the blank group( P < 0. 01). Compared with the model group,the levels of SOD1,SOD2 and MDA of the serum and the gastric issue were increased in the high-dose,middle-dose and low-dose YWXY groups( P < 0. 01,P <0. 05). The levels of serum SOD2 were increased in the high-dose and the low-dose group( P < 0. 01). Compared with the blank group,MDA level of serum and gastric mucosa were increased in the model group( P < 0. 01). Compared with the model group,the levels of MDA of serum and gastric mucosa were all reduced in the high-dose,middle-dose and low-dose YWXY groups( P < 0. 01). Conclusion YWXY improves in the intestinal metaplasia in the rats with atrophic gastritis,which is probably related to the inhibition of NF-k B expression,the decrease of TNF-α,IL-1β and MDA levels and the increase of GAS,SOD1 and SOD2 levels.
Objective To observe the effects of yiwei xiaoyu granules( YWXY) on intestinal metaplasia of gastric mucosa and the related inflammatory mediators of the gastric tissue in the rats and analyze the potential mechanism of this drug in the treatment of intestinal metaplasia of gastric mucosa. Methods A total of 60 female SD rats,8 weeks in age were collected and divided into a blank group,a model group,a high-dose YWXY group,a middle-dose YWXY group,a low-dose YWXY group and a weifucun( WFC) group,10 rats in each one according to the random number table. N-methyl-N'-nitro-N-nitroso guanidine was adopted for modeling. Separately,in 6 and 7 months,3 rats were randomly checked. After modeling success,the drug intervention started. After medication for 3 months,the histological changes of the gastric tissue were observed. ELISA method was used to determine the levels of TNF-α,IL-1β,GAS,SOD and MDA. RT-q PCR was adopted to determine the expression of NF-κB in the sample of gastric mucosa. Results Under microscope,the mucosal atrophy and intestinal metaplasia were visible in the model group. The mucosal atrophy and intestinal metaplasia were relieved obviously in the high-dose and middle-dose YWXY groups as compared with the model group. The mucosal atrophy and intestinal metaplasia were reduced in the low-dose group and WFC group as compared with the model group. NF-κB expression in the gastric mucosa in the model group was increased as compared with theblank group( P < 0. 01). The levels of TNF-α in serum and gastric mucosa in the model group were all increased as compared with the blank group( P < 0. 01). Compared with the model group,the levels of TNF-α in serum were reduced in the high-dose and middle dose YWXY group( P < 0. 01). The levels of IL-1β of the serum and the gastric issue in the model group were increased as compared with the blank group( P < 0. 01). Compared with the model group,the levels of IL-1β of the serum and the gastric issue were reduced in the high-dose,middle-dose and low-dose YWXY groups( P <0. 01,P < 0. 05). The differences in SOD1,SOD2 and MDA of the serum and the gastric issue were significant between the model group and the blank group( P < 0. 01). Compared with the model group,the levels of SOD1,SOD2 and MDA of the serum and the gastric issue were increased in the high-dose,middle-dose and low-dose YWXY groups( P < 0. 01,P <0. 05). The levels of serum SOD2 were increased in the high-dose and the low-dose group( P < 0. 01). Compared with the blank group,MDA level of serum and gastric mucosa were increased in the model group( P < 0. 01). Compared with the model group,the levels of MDA of serum and gastric mucosa were all reduced in the high-dose,middle-dose and low-dose YWXY groups( P < 0. 01). Conclusion YWXY improves in the intestinal metaplasia in the rats with atrophic gastritis,which is probably related to the inhibition of NF-k B expression,the decrease of TNF-α,IL-1β and MDA levels and the increase of GAS,SOD1 and SOD2 levels.
引文
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[11]Tahara T,Shibata T,Yamashita H. Synergistic effect of IL-1βand TNF-αpolymorphisms on the Hpylori-related gastric pre-malignant condition[J]. Hepatogastroenterology,2012,59(59):2416-2420.
[12]冯果,武静,陈继婷,等.健脾温胃散对脾气虚胃炎大鼠血清TNF-α,IL-6及胃组织IRAK-4 mRNA表达的影响[J].中国实验方剂学杂志,2016(14):145-150.
[13]林海燕,于佳宁,翟佳丽,等.萎胃康对萎缩性胃炎大鼠血清IL-6,IL-10含量及胃黏膜NF-κB表达的影响[J].中国中西医结合消化杂志,2016(12):898-901.
[14]江梅,李汀,张沥,等.热盐水致大鼠萎缩性胃炎血清和胃黏膜组织SOD和MDA的动态变化[J].中国消化内镜杂志,2009(2):34-38.
[15]Xiao YJ,Li PQ,Xiao JZ,et al. Interventional effect of Ginkgo biloba,extract on the progression of gastric precancerous lesions in rats[J]. Journal of Digestive Diseases,2009,10(4):293-299.
[16]舒劲,李喜香,任远,等.制萎扶胃浓缩丸对慢性萎缩性胃炎模型大鼠SOD活性、MDA和NO含量的影响[J].中国实验方剂学杂志,2011,17(2):160-162.
[17]谢晶日,葛阳,张杨.欣胃颗粒对慢性萎缩性胃炎大鼠血清胃泌素的影响[J].中医药学报,2013,41(3):88-89.
[2]WalkerM M. Is intestinal metaplasia of the stomach reversible?[J].Gut,2003,52(1):1-4.
[3]吴莉佳,谢慧民,田锋亮,等.益胃消瘀颗粒治疗慢性萎缩性胃炎30例[J].中国中西医结合消化杂志,2007,15(1):57-59.
[4]郑筱萸.中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002:125-129.
[5]中华中医药学会脾胃病分会.慢性萎缩性胃炎中医诊疗共识意见[J].中国中西医结合消化杂志,2010,18(5):749-753.
[6]张越亚,杨国红.慢性萎缩性胃炎癌前病变中医药研究进展[J].中医临床研究,2017,9(2):146-148.
[7]季梅,杨进.慢性萎缩性胃炎的中医药研究进展[J].湖南中医杂志,2015,31(4):176-179.
[8]Shifera AS. The zinc finger domain of IKKγ(NEMO)protein in health and disease[J]. Journal of Cellular&Molecular Medicine,2010,14(10):2404-2414.
[9]Marusawa H,Takai A,Chiba T. Role of activation-induced cytidine deaminase in inflammation-associated cancer development[J]. Advances in Immunology,2011(111):109-141.
[10]Shimizu T,Marusawa H,Endo Y,et al. Inflammation-mediated genomic instability:roles of activation-induced cytidine deaminase in carcinogenesis[J]. Cancer Science,2012,103(7):1201-1206.
[11]Tahara T,Shibata T,Yamashita H. Synergistic effect of IL-1βand TNF-αpolymorphisms on the Hpylori-related gastric pre-malignant condition[J]. Hepatogastroenterology,2012,59(59):2416-2420.
[12]冯果,武静,陈继婷,等.健脾温胃散对脾气虚胃炎大鼠血清TNF-α,IL-6及胃组织IRAK-4 mRNA表达的影响[J].中国实验方剂学杂志,2016(14):145-150.
[13]林海燕,于佳宁,翟佳丽,等.萎胃康对萎缩性胃炎大鼠血清IL-6,IL-10含量及胃黏膜NF-κB表达的影响[J].中国中西医结合消化杂志,2016(12):898-901.
[14]江梅,李汀,张沥,等.热盐水致大鼠萎缩性胃炎血清和胃黏膜组织SOD和MDA的动态变化[J].中国消化内镜杂志,2009(2):34-38.
[15]Xiao YJ,Li PQ,Xiao JZ,et al. Interventional effect of Ginkgo biloba,extract on the progression of gastric precancerous lesions in rats[J]. Journal of Digestive Diseases,2009,10(4):293-299.
[16]舒劲,李喜香,任远,等.制萎扶胃浓缩丸对慢性萎缩性胃炎模型大鼠SOD活性、MDA和NO含量的影响[J].中国实验方剂学杂志,2011,17(2):160-162.
[17]谢晶日,葛阳,张杨.欣胃颗粒对慢性萎缩性胃炎大鼠血清胃泌素的影响[J].中医药学报,2013,41(3):88-89.