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纸质出版日期:2017
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汪蕾, Nuriza Rahmadini, 高天慧, 等. 印尼姜黄对刀豆球蛋白A所致小鼠肝损伤的保护作用及其影响TGF-/Smad通路的机制探讨[J]. 中国实验方剂学杂志, 2017,23(7):127-133.
WANG Lei, GAO Tian-hui, YU Jia-li, et al. Protective Effect of Rhizome on Hepatitis Induced by Concanavalin A in Mice and Effect on TGF-/Smad Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(7): 127-133.
汪蕾, Nuriza Rahmadini, 高天慧, 等. 印尼姜黄对刀豆球蛋白A所致小鼠肝损伤的保护作用及其影响TGF-/Smad通路的机制探讨[J]. 中国实验方剂学杂志, 2017,23(7):127-133. DOI: 10.13422/j.cnki.syfjx.2017070127.
WANG Lei, GAO Tian-hui, YU Jia-li, et al. Protective Effect of Rhizome on Hepatitis Induced by Concanavalin A in Mice and Effect on TGF-/Smad Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(7): 127-133. DOI: 10.13422/j.cnki.syfjx.2017070127.
目的:研究印尼姜黄对刀豆蛋白A(Con A)诱导的小鼠肝损伤的保护作用,并探究其可能机制。方法: SPF级小鼠随机分为正常组、模型组、联苯双酯阳性药组及印尼姜黄高、中、低剂量组。灌胃给药7 d,末次给药后2 h除正常组外,其余各组小鼠均一次性尾静脉注射Con A 30 mg·kg-1诱导小鼠肝损伤,禁食不禁水8 h后称量体重,摘眼球取血并脱颈椎处死动物,计算小鼠的肝脏、脾脏指数,检测血清丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),乳酸盐脱氢酶(LDH)活性及肝组织匀浆中总超氧化物歧化酶(T-SOD),丙二醛(MDA),一氧化氮(NO)的含量,苏木素-伊红(HE)观察肝组织病理学变化,采用实时荧光定量PCR(Real-time PCR)和蛋白质免疫印迹法(Western blot)检测肝脏转化生长因子-β1(TGF-β1),Smad3,Smad7的mRNA和蛋白表达。结果:与正常组比较,模型组肝脏、脾脏指数、血清中ALT,AST,LDH及肝匀浆MDA,NO的水平显著升高,肝匀浆T-SOD水平显著降低,肝脏组织中TGF-β1,Smad3的mRNA及蛋白表达显著升高,Smad7的mRNA和蛋白表达显著降低(P<0.01),模型组的肝脏病变较为明显;与模型组比较,印尼姜黄与联苯双酯均可明显降低肝炎小鼠的肝脏、脾脏指数,降低血清中ALT,AST,LDH及肝匀浆MDA,NO的水平,肝匀浆T-SOD水平明显升高;印尼姜黄高剂量组肝脏病理改变明显减轻,印尼姜黄高剂量组的小鼠肝脏组织中TGF-β1,Smad3的mRNA及蛋白表达下降,Smad7的mRNA和蛋白表达升高(P<0.05,P<0.01)。结论:印尼姜黄对Con A诱导的小鼠肝损伤具有显著保护作用,通过多位点影响肝组织TGF-β1/Smad通路可能是其阻断肝损伤进程的机制。
Objective: To study the protective effects of Curcuma zanthorrhiza rhizome on liver injury induced by concanavalin A(Con A) in mice
and investigate its possible mechanism. Method: SPF mice were randomly divided into normal group
model group
biphenyl group
C. zanthorrhiza rhizome high dose group
middle dose group and low dose group. All the mice except those in normal group received Con A (30 mg·kg-1) by injection via tail vein to induce mice liver injury. The drugs were given for 7 days by gavage administration
and the mice in normal group received the equal volume of normal saline. After fasting (but water was given) for 8 h
their body weight was measured; blood was taken from eyeball
and the mice were killed by taking off the cervical vertebrae. Then their liver index
spleen index
contents of alanine aminotransferase (ALT)
aspartate amino transferase (AST)
and lactate dehydrogenase (LDH) in serum and total superoxide dismutase (T-SOD)
malondialdehyde (MDA)
nitric oxide (NO) in liver homogenates were measured. Hepatic tissue was observed by hematoxylin-eosin staining. Furthermore
real-time fluorescence quantitative PCR (Real-time PCR) and Western blot assay were used to detect mRNA and protein expression levels of liver tramsforming gravth factor-β1(TGF-β1)
Smad3 and Smad7. Result: As compared with the normal group
the liver index
spleen index
levels of ALT
AST and LDH in serum as well as MDA and NO levels in liver homogenates were significantly increased in model group; T-SOD level in liver homogenates was significantly reduced; mRNA and protein expression levels of liver TGF-β1
Smad3 were significantly increased
while mRNA and protein expression levels of Smad3 were significantly reduced (P<0.01)
with more obvious liver lesions in model group. As compared with the model group
both C. zanthorrhiza rhizome and biphenyl significantly reduced the liver index and spleen index; decreased the levels of ALT
AST
LDH in serum and MDA
NO levels in liver homogenates; and significantly increased T-SOD level in liver homogenates. The liver lesions were significantly relieved in C. zanthorrhiza rhizome high dose group
mRNA and protein expression levels of liver TGF-β1
Smad3 were reduced
while mRNA and protein expression levels of Smad3 were increased (P<0.05
P<0.01). Conclusion: Curcuma zanthorrhiza rhizome had significant protective effect for the liver injury induced by Con A
and its mechanism to block the progression of liver injury may be associated with multi-site affecting TGF-β1/Smad pathways in liver tissues.
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