豆类丝核菌次级代谢产物对免疫抑制小鼠免疫功能的影响
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摘要
目的:研究豆类丝核菌次级代谢产物对环磷酰胺(Cyclophosphamide,CTX)所致免疫抑制小鼠免疫功能的影响。采用腹腔注射CTX诱导昆明小白鼠免疫抑制模型。通过外周血白细胞数、脏器指数、腹腔巨噬细胞吞噬功能、外周血中溶血素水平、脾脏淋巴细胞转化、NK细胞杀伤活性、脾细胞IL-2的活性及病理学观察等方面研究,探索两者联合应用对小鼠免疫功能的影响,为该代谢产物在今后临床应用提供新的思路。
方法:①分别给小白鼠腹腔注射80 mg/kg的CTX,每日一次,共三次建立能够造成免疫抑制的动物模型。②给小白鼠注射CTX的同时灌胃豆类丝核菌次级代谢产物,其苦马豆素(Swainsonine,SW)剂量分别为8、16、32 mg/kg,将豆类丝核菌次级代谢产物与CTX两者联合应用,随机均分为5组:Ⅰ组(正常对照组);Ⅱ组(CTX对照组);Ⅲ组(SW 8 mg/kg + CTX 80 mg/kg);Ⅳ组(SW 16 mg/kg + CTX 80 mg/kg);Ⅴ组(SW 32 mg/kg + CTX 80 mg/kg),末次用药24h后检查外周血白细胞数、脏器指数、腹腔巨噬细胞吞噬功能、外周血中溶血素水平、脾脏淋巴细胞转化、NK细胞杀伤活性。探索豆类丝核菌次级代谢产物对CTX所致小鼠免疫抑制的免疫功能的影响及可能机制,并确定保护剂量。最后剖检动物取肝脏、肾脏进行病理组织学观察。
结果:腹腔注射CTX80 mg/kg,连续3天,可致小鼠免疫抑制,剂量为8、16 mg/ (kg·d)的SW组均可提高小鼠的外周血白细胞数,颉颃环磷酰胺所致的小鼠腹腔巨噬细胞吞噬功能的降低,提高外周血中溶血素水平、脾脏淋巴细胞转化以、脾细胞IL-2的活性及NK细胞杀伤活性,尤其以SW16 mg/ (kg·d)最为明显。
结论:①CTX以80 mg/kg连续腹腔注射3次可以造成小鼠免疫抑制。②豆类丝核菌次级代谢产物(SW剂量为8、16 mg/kg)对CTX致免疫抑制具有一定的有一定的恢复和增强作用。
Objectives:This trial was to study the effects of the secondary metabolites of Rhizotonia leguminicola on cyclophosphamide (CTX)-induced immunoregulation of immunosuppressed mice. The immunosuppression model was established by CTX injected into abdominal cavity of the KunMing Mus musculus albus. The number of PWBC, index of organ, phagocytic activity of peritoneal macrophage, hemolysin level in peripheral blood, lymphocyte transformation of spleen, activity of NK cells were measured and pathology changes were observed to explore the effect of immune function of mice on both union application. All these could provide rationale for the secondary metabolites in clinical application.
Methods:①The mice were injected intraperitoneally with 80 mg/kg CTX everyday, three times consecutive, to establish the animal model which could result in immunosuppression.②The mice were infused CTX and the secondary metabolites of Rhizoctonia leguminicola which had swainsonine respectively at 8,16,32 mg/kg. The secondary metabolites of Rhizoctonia leguminicola and CTX were jointly utilized and were divided into 5 groups randomly: groupⅠ(normal saline), groupⅡ(CTX 100 mg/kg), groupⅢ(SW8 mg/kg + CTX 80 mg/kg), groupⅣ(SW16 mg/kg + CTX 80 mg/kg), groupⅤ(SW32 mg/kg + CTX 80 mg/kg); 24h after the last administration, The number of PWBC, index of organ, phagocytic activity of peritoneal macrophage, hemolysin level in peripheral blood, lymphocyte transformation of spleen, activity of NK cells were measured. This trial was to explore the effects of secondary metabolites of Rhizotonia leguminicola on the immune function of CTX-induced immunosuppressive mice and the possible mechanism, and to obtain the safeguard dose. In the end, animals were dissected to observe the histopathology in liver and kidney.
Results: CTX was injected consecutively into the abdominal cavity at 80 mg/kg for 3d, which leaded to immunosuppression for the mice. The groups which contained SW at 8 and 16 mg/ (kg·d) could increase the number of PWBC of the mice. The CTX induced a decrease in phagocytic activity of peritoneal macrophage of mice and a boost of hemolysin level in peripheral blood, lymphocyte transformation of spleen and the activity of NK cells, which is especially workable for the group contained SW at 16 mg/(kg·d).
Conclusion:①CTX was injected consecutively into the abdominal cavity at 80 mg/kg for 3d, which leaded to immunosuppression for the mice.②The secondary metabolites of Rhizotonia leguminicola (the dose of SW at 8,16 mg/kg) has effects on the recovery and reinforcement of CTX-induced immunosuppression.
方法:①分别给小白鼠腹腔注射80 mg/kg的CTX,每日一次,共三次建立能够造成免疫抑制的动物模型。②给小白鼠注射CTX的同时灌胃豆类丝核菌次级代谢产物,其苦马豆素(Swainsonine,SW)剂量分别为8、16、32 mg/kg,将豆类丝核菌次级代谢产物与CTX两者联合应用,随机均分为5组:Ⅰ组(正常对照组);Ⅱ组(CTX对照组);Ⅲ组(SW 8 mg/kg + CTX 80 mg/kg);Ⅳ组(SW 16 mg/kg + CTX 80 mg/kg);Ⅴ组(SW 32 mg/kg + CTX 80 mg/kg),末次用药24h后检查外周血白细胞数、脏器指数、腹腔巨噬细胞吞噬功能、外周血中溶血素水平、脾脏淋巴细胞转化、NK细胞杀伤活性。探索豆类丝核菌次级代谢产物对CTX所致小鼠免疫抑制的免疫功能的影响及可能机制,并确定保护剂量。最后剖检动物取肝脏、肾脏进行病理组织学观察。
结果:腹腔注射CTX80 mg/kg,连续3天,可致小鼠免疫抑制,剂量为8、16 mg/ (kg·d)的SW组均可提高小鼠的外周血白细胞数,颉颃环磷酰胺所致的小鼠腹腔巨噬细胞吞噬功能的降低,提高外周血中溶血素水平、脾脏淋巴细胞转化以、脾细胞IL-2的活性及NK细胞杀伤活性,尤其以SW16 mg/ (kg·d)最为明显。
结论:①CTX以80 mg/kg连续腹腔注射3次可以造成小鼠免疫抑制。②豆类丝核菌次级代谢产物(SW剂量为8、16 mg/kg)对CTX致免疫抑制具有一定的有一定的恢复和增强作用。
Objectives:This trial was to study the effects of the secondary metabolites of Rhizotonia leguminicola on cyclophosphamide (CTX)-induced immunoregulation of immunosuppressed mice. The immunosuppression model was established by CTX injected into abdominal cavity of the KunMing Mus musculus albus. The number of PWBC, index of organ, phagocytic activity of peritoneal macrophage, hemolysin level in peripheral blood, lymphocyte transformation of spleen, activity of NK cells were measured and pathology changes were observed to explore the effect of immune function of mice on both union application. All these could provide rationale for the secondary metabolites in clinical application.
Methods:①The mice were injected intraperitoneally with 80 mg/kg CTX everyday, three times consecutive, to establish the animal model which could result in immunosuppression.②The mice were infused CTX and the secondary metabolites of Rhizoctonia leguminicola which had swainsonine respectively at 8,16,32 mg/kg. The secondary metabolites of Rhizoctonia leguminicola and CTX were jointly utilized and were divided into 5 groups randomly: groupⅠ(normal saline), groupⅡ(CTX 100 mg/kg), groupⅢ(SW8 mg/kg + CTX 80 mg/kg), groupⅣ(SW16 mg/kg + CTX 80 mg/kg), groupⅤ(SW32 mg/kg + CTX 80 mg/kg); 24h after the last administration, The number of PWBC, index of organ, phagocytic activity of peritoneal macrophage, hemolysin level in peripheral blood, lymphocyte transformation of spleen, activity of NK cells were measured. This trial was to explore the effects of secondary metabolites of Rhizotonia leguminicola on the immune function of CTX-induced immunosuppressive mice and the possible mechanism, and to obtain the safeguard dose. In the end, animals were dissected to observe the histopathology in liver and kidney.
Results: CTX was injected consecutively into the abdominal cavity at 80 mg/kg for 3d, which leaded to immunosuppression for the mice. The groups which contained SW at 8 and 16 mg/ (kg·d) could increase the number of PWBC of the mice. The CTX induced a decrease in phagocytic activity of peritoneal macrophage of mice and a boost of hemolysin level in peripheral blood, lymphocyte transformation of spleen and the activity of NK cells, which is especially workable for the group contained SW at 16 mg/(kg·d).
Conclusion:①CTX was injected consecutively into the abdominal cavity at 80 mg/kg for 3d, which leaded to immunosuppression for the mice.②The secondary metabolites of Rhizotonia leguminicola (the dose of SW at 8,16 mg/kg) has effects on the recovery and reinforcement of CTX-induced immunosuppression.
引文
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