小半夏汤对顺铂导致的大鼠胃肠道炎症损伤的防治作用
|
摘要
目的观察小半夏汤对化疗大鼠胃肠道炎症损伤的防治作用,并初步探讨其作用机制。方法取Wistar大鼠随机分为空白对照组、小半夏汤正常对照组(1.6 g·kg~(-1)·d~(-1))、顺铂模型组、阳性药对照组(奥美拉唑2.4mg·kg~(-1)·d-1)和小半夏汤低、中、高剂量组(0.8,1.6,3.2 g·kg~(-1)·d~(-1))。大鼠腹腔注射(i.p.)顺铂6 mg·kg~(-1)造模,造模前2 d灌胃(i.g.)给药,连续5 d。造模后24 h和72 h两个时间点下腔静脉取血,ELSA法检测血清中肿瘤坏死因子(TNF-ɑ)、白介素-1β(IL-1β)、前列腺素E(2PGE_2);取胃窦和回肠组织,常规石蜡切片,HE染色观察组织病理变化,免疫组化法检测胃窦和回肠组织中核转录因子(NF-κB)、环氧合酶-2(COX-2)表达情况。结果模型组大鼠胃肠黏膜可见炎性病理改变,造模72 h,血清中TNF-ɑ、IL-1β、PGE_2水平均显著升高,差异有统计学意义(P<0.001),胃肠组织中NF-κB、COX-2阳性表达显著升高;小半夏汤能改善化疗动物胃肠道炎症程度,小半夏汤中、高剂量组能显著降低化疗大鼠24 h和72 h血清中TNF-ɑ、PGE_2水平,显著降低化疗大鼠72 h血清中IL-1β水平,差异有统计学意义(P<0.05,P<0.01,P<0.001),并能显著减少胃窦、回肠组织在24 h、72 h NF-κB、COX-2的阳性表达。结论小半夏汤能防治化疗药物导致的大鼠胃肠炎症损伤,其作用机制可能与抑制炎性因子表达有关。
Objective To investigate the mechanism of protective effect of Xiao Ban Xia Tang(XBXT) on chemotherapy-induced gastrointestinal tract inflammatory injury in rats. Methods The chemotherapy rat model was established by intraperitoneal injection of 6 mg·kg~(-1)cisplatin. Wistar rats were randomly divided into normal group,XBXT normal control group, cisplatin model group, positive drug omeprazole group, XBXT low-, middle-,high-dose groups. From 2 days before modeling,rats in omeprazole group,XBXT normal control group,XBXT low-,middle-and high-dose groups were given 2.4 mg·kg~(-1)·d~(-1) omeprazole, 0.8, 1.6 and 3.2 g·kg~(-1)·d~(-1) XBXT by oral gavage respectively,twice per day,for 5 days. The rats in normal control group and model group were gavaged with equal volume of distilled water. After modeling 24 h and 72 h, TNF-α,IL-1β and PGE_2 in serum were measured by ELISA. The NF-κB,COX-2 in rat sinuses ventriculi and ileum were detected by immunohistochemistry method,and sinuses ventriculi and ileum were visualized by hematoxylin and eosin staining. Results Inflammatory pathological changes were observed in the rats' GI mucosa in cisplatin model group, and levels of TNF-α, IL-1β, PGE_2 increased significantly in serum(P<0.05);NF-κB,COX-2 expression levels were significantly higher than that in normal group in sinuses ventriculi and ileum after modeling 72 h. XBXT can improve chemotherapy rats' gastrointestinal inflammation, that the middle-and high-dosages of XBXT significantly reduced the levels of TNF-α,PGE_2 at 24 h and 72 h in cisplatin-treated serum. IL-1β decreased significantly at 72 h in cisplatin-treated serum(P<0.05),and significantly reduced the positive expression of NF-κB,COX-2 in gastric and ileum tissue at 72 h. Conclusion XBXT can prevent and treat the gastrointestinal inflammatory injury induced by cisplatin in rats, and the mechanism may be related to the inhibition of inflammatory factor expression.
Objective To investigate the mechanism of protective effect of Xiao Ban Xia Tang(XBXT) on chemotherapy-induced gastrointestinal tract inflammatory injury in rats. Methods The chemotherapy rat model was established by intraperitoneal injection of 6 mg·kg~(-1)cisplatin. Wistar rats were randomly divided into normal group,XBXT normal control group, cisplatin model group, positive drug omeprazole group, XBXT low-, middle-,high-dose groups. From 2 days before modeling,rats in omeprazole group,XBXT normal control group,XBXT low-,middle-and high-dose groups were given 2.4 mg·kg~(-1)·d~(-1) omeprazole, 0.8, 1.6 and 3.2 g·kg~(-1)·d~(-1) XBXT by oral gavage respectively,twice per day,for 5 days. The rats in normal control group and model group were gavaged with equal volume of distilled water. After modeling 24 h and 72 h, TNF-α,IL-1β and PGE_2 in serum were measured by ELISA. The NF-κB,COX-2 in rat sinuses ventriculi and ileum were detected by immunohistochemistry method,and sinuses ventriculi and ileum were visualized by hematoxylin and eosin staining. Results Inflammatory pathological changes were observed in the rats' GI mucosa in cisplatin model group, and levels of TNF-α, IL-1β, PGE_2 increased significantly in serum(P<0.05);NF-κB,COX-2 expression levels were significantly higher than that in normal group in sinuses ventriculi and ileum after modeling 72 h. XBXT can improve chemotherapy rats' gastrointestinal inflammation, that the middle-and high-dosages of XBXT significantly reduced the levels of TNF-α,PGE_2 at 24 h and 72 h in cisplatin-treated serum. IL-1β decreased significantly at 72 h in cisplatin-treated serum(P<0.05),and significantly reduced the positive expression of NF-κB,COX-2 in gastric and ileum tissue at 72 h. Conclusion XBXT can prevent and treat the gastrointestinal inflammatory injury induced by cisplatin in rats, and the mechanism may be related to the inhibition of inflammatory factor expression.
引文
[1]聂克,马素起.小半夏汤对化疗性大鼠异食癖的防治作用[J].中药药理与临床,2007,23(5):32-33.
[2]于功昌,张勇,杜秀伟,等.小半夏汤对化疗性异食癖大鼠P物质和NK1受体的影响[J].中药药理与临床,2015,31(1):17-20.
[3]SONIS ST.Regimen-related gastrointestinal toxicities in cancer patients[J].Current Opinion in Supportive and Palliative Care,2010,4:26-30.
[4]LOGAN RM,STRINGER AM,BOWEN JM,et al.Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered[J].Cancer chemotherapy and pharmacology,2009,63(2):239-251.
[5]欧阳学农,戴西湖,陈曦,倪敏.恩丹西酮并用小半夏汤预防肿瘤化疗所致呕吐的临床观察[J].中国中西医结合杂志,2002,22(4):312.
[6]蒋淳琪,刘文奇,山广志.小半夏汤治疗化疗后呕吐临床研究[J].黑龙江中医药,2013,42(2):20-21.
[2]于功昌,张勇,杜秀伟,等.小半夏汤对化疗性异食癖大鼠P物质和NK1受体的影响[J].中药药理与临床,2015,31(1):17-20.
[3]SONIS ST.Regimen-related gastrointestinal toxicities in cancer patients[J].Current Opinion in Supportive and Palliative Care,2010,4:26-30.
[4]LOGAN RM,STRINGER AM,BOWEN JM,et al.Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered[J].Cancer chemotherapy and pharmacology,2009,63(2):239-251.
[5]欧阳学农,戴西湖,陈曦,倪敏.恩丹西酮并用小半夏汤预防肿瘤化疗所致呕吐的临床观察[J].中国中西医结合杂志,2002,22(4):312.
[6]蒋淳琪,刘文奇,山广志.小半夏汤治疗化疗后呕吐临床研究[J].黑龙江中医药,2013,42(2):20-21.