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穿龙薯蓣皂苷对再生障碍性贫血小鼠PPAR
γ ，C/EBPα 及脂肪分泌因子表达的影响Effect of Diosgenin on Expressions of PPARγ, C/EBPα and Adipokine Secretion in Aplastic Anemia Mice
- 中国实验方剂学杂志 2019年25卷第5期 页码：126-134
- 作者机构：
1.天津医科大学 总医院，天津 300052；
2.天津中医药大学 研究生院，天津 300193
- 作者简介：
张珊，在读硕士，从事中西医结合血液病研究，E-mail: 1174677183@qq.com
刘宝山，博士生导师，教授，从事中西医结血液病研究，E-mail: j33387@qq.com
- 基金信息：天津医科大学“十三五”综合投资学科建设项目(11601502-XK0135);国家自然科学基金重点项目(81774062;81173415)
DOI：10.13422/j.cnki.syfjx.20190503
中图分类号： R2-0;R22;R285.5收稿日期：2018-07-29，
网络出版日期：2018-11-21，
纸质出版日期：2019-03-05
- 稿件说明：
移动端阅览
张珊, 尹立祥, 王爱迪, 等. 穿龙薯蓣皂苷对再生障碍性贫血小鼠PPAR
γ ，C/EBPα 及脂肪分泌因子表达的影响[J]. 中国实验方剂学杂志, 2019,25(5):126-134.Shan ZHANG, Li-xiang YIN, Ai-di WANG, et al. Effect of Diosgenin on Expressions of PPARγ, C/EBPα and Adipokine Secretion in Aplastic Anemia Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 126-134.
张珊, 尹立祥, 王爱迪, 等. 穿龙薯蓣皂苷对再生障碍性贫血小鼠PPAR
γ ，C/EBPα 及脂肪分泌因子表达的影响[J]. 中国实验方剂学杂志, 2019,25(5):126-134. DOI： 10.13422/j.cnki.syfjx.20190503.Shan ZHANG, Li-xiang YIN, Ai-di WANG, et al. Effect of Diosgenin on Expressions of PPARγ, C/EBPα and Adipokine Secretion in Aplastic Anemia Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 126-134. DOI： 10.13422/j.cnki.syfjx.20190503.
摘要
目的：
2
观察穿龙薯蓣皂苷对再生障碍性贫血小鼠的治疗作用及其对过氧化物酶体增殖物激活受体
γ
(peroxisome proliferator activated receptor
γ
PPAR
γ
)，CCATT增强子结合蛋白
α
(CCAAT-enhancer binding protein
α
C/EBP
α
)，脂联素(Adiponectin)，瘦素(Leptin)的影响，探究其在骨髓间充质干细胞脂肪化过程中发挥效应的可能机制。
方法：
2
BALB/c小鼠随机分为正常组及模型组，模型组小鼠经
60
Coy照射联合尾静脉输注DBA/2小鼠淋巴细胞混悬液法造模。模型评估成功后，将成模小鼠随机分为6组，分别为模型组，穿龙薯蓣皂苷低、中、高剂量组(37.44
74.88
149.76mg·kg
－1
·d
－1
)，环孢素组(23.5mg·kg
－1
·d
－1
)，雷公藤多苷组(9.36mg·kg
－1
·d
－1
)，相应药物灌胃14d。干预完成后，检测各组小鼠外周血象并制作骨髓细胞涂片评价骨髓增生情况。采用贴壁法分离培养各组小鼠骨髓间充质干细胞(bone marrow mesenchymal stem cells
BMMSCs)并进行成脂诱导；采用实时荧光定量聚合酶链式反应(Real-time PCR)，蛋白免疫印迹法(Western blot)检测各组小鼠BMMSCs中PPAR
γ
，C/EBP
α
，Adiponectin
LeptinmRNA和蛋白表达。
结果：
2
与正常组比较，模型组小鼠外周血白细胞(white blood cell
WBC)，血红蛋白(hemoglobin
HGB)，血小板(blood platelet
PLT)明显降低(
P
<
0.05)；与模型组比较，各治疗组小鼠血象均有不同程度回升，以穿龙薯蓣中剂量组最优(
P
<
0.05)。与正常组比较，模型组小鼠BMMSCs中PPAR
γ
，C/EBP
α
，Adiponectin
Leptin mRNA和蛋白表达明显升高(
P
<
0.05)；与模型组比较，各治疗组小鼠上述指标均被不同程度抑制，其中穿龙薯蓣皂苷中剂量组和环孢素组PPAR
γ
，C/EBP
α
，Adiponectin
Leptin mRNA和蛋白表达明显下调，优于雷公藤多苷组(
P
<
0.05)。
结论：
2
穿龙薯蓣皂苷能够促进再障小鼠外周血象恢复，改善骨髓造血。穿龙薯蓣皂苷可抑制AA小鼠BMMSCs PPAR
γ
，C/EBP
α
的表达，减少脂肪细胞分泌的Adiponectin
Leptin，进而有效地抑制BMMSCs向脂肪细胞的过度分化。
Abstract
Objective:
2
To observe the effect of diosgenin on aplastic anemia (AA) mice and peroxisome proliferator activated receptor
γ
(PPAR
γ
)
CCAAT-enhancer binding protein
α
(C/EBP
α
)
Adiponectin
Leptin
in order to discuss the potential mechanism of bone marrow mesenchymal stem cells in the process of adipemia.
Method:
2
BALB/c mice were randomly divided into control group and model group. The model group was established by
60
Coy irradiation combined with tail vein infusion with lymphatic suspension cells of DBA/2 mice. After successful evaluation of the model
the mice were randomly divided into 6groups: model group
low
medium and high-dose diosgenin groups (37.44
74.88
149.76mg·kg
-1
·d
-1
)
cyclosporine group (23.5mg·kg
-1
·d
-1
)
and tripterygium glycoside group (9.36mg·kg
-1
·d
-1
)
and given corresponding drugs by gavage for 14days. After the intervention
the peripheral blood of mice in each group was detected
and bone marrow smears were collected to evaluate the proliferation of bone marrow. Bone marrow mesenchymal stem cells (BMMSCs) were isolated and cultured by adherent method and induced by adipogenesis. ThemRNA and protein expressions of PPAR
γ
C/EBP
α
Adiponectin
Leptin in BMMSCs were detected by quantitative real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) and Western blot.
Result:
2
The white blood cell (WBC)
hemoglobin (HGB) and blood platelet (PLT) in peripheral blood of model group were significantly lower than those of normal group (
P
<
0.05). The hemogram of each treatment group was higher than that of model group to varying degrees. The middle-dose Dioscorea nipponica group had the most obvious hemogram
with statistically significant differences compared with the model group (
P
<
0.05). Compared with the control group
the mRNA and protein expressions of PPAR
γ
C/EBP
α
Adiponectin and Leptin in BMMSCs of the model group increased significantly (
P
<
0.05). Compared with the model group
the above indexes in the treatment groups were all decreased
the mRNA and protein expressions of PPAR
γ
C/EBP
α
Adiponectin and Leptin in the middle-dose group diosgenin decreased obviously
which was better than those of Tripterygium glycoside group (
P
<
0.05).
Conclusion:
2
Diosgenin can promote the recovery of peripheral blood in aplastic anemia mice and improve the hematopoiesis of bone marrow. Diosgenin can reduce the expressions of PPAR
γ
and C/EBP
α
the formation of adipocytes and the secretion of Adiponectin and Leptin in adipocytes
and effectively inhibit the process of adipose tissue derived from bone BMMSCs.
关键词
Keywords
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