紫杉醇对牛血清白蛋白诱导大鼠肝纤维化的抑制作用及机制
| 作者: |
1边虹铮,
1刘丽芳
1 河北化工医药职业技术学院 制药工程系，河北 石家庄 050031 |
| 通讯: |
边虹铮
Email: 3166001899@qq.com |
| DOI: | 10.3978/.2018.08.010 |
摘要
目的：探讨紫杉醇对牛血清白蛋白（BSA）诱导大鼠肝纤维化的抑制作用及机制。
方法：用 BSA 诱导 Wistar 大鼠产生免疫性肝纤维化后，分别通过尾静脉注射生理盐水（模型组）与10 μg/g 紫杉醇（紫杉醇处理组），另取 10 只正常大鼠以相同的方式注射生理盐水作为对照组。每天注射 1 次，28 d 后处死大鼠获取血与肝组织标本，行肝组织病理学观察，检测血清肝功能生化指标与血清及肝组织胶原相关指标、肝组织 α-SMA、TGF-β1 表达，分离肝星状细胞（HSC），检测 HSC中 TGF-β/Smad 信号通路相关分子的蛋白及 mRNA 的表达。
结果：与对照组比较，模型组出现明显的肝纤维化改变、血清转氨酶水平明显升高，而白蛋白水平明显降低、血清与肝组织胶原相关指标明显升高、肝组织 α-SMA 与 TGF-β1 表达率明显升高、HSC 中TGF-β/Smad 信号通路相关分子的蛋白及 mRNA 明显上调（均 P<0.05）。紫杉醇处理组以上指标的变化程度均明显小于模型组（均 P<0.05），且部分指标与对照组无明显差异（部分 P>0.05）。
结论：紫杉醇对 BSA 诱导大鼠免疫性肝纤维化有抑制作用，机制可能与其抑制 TGF-β/Smad 信号传导通路活化有关。
关键词：
肝硬化；紫杉酚；转化生长因子 β；疾病模型，动物；大鼠
方法：用 BSA 诱导 Wistar 大鼠产生免疫性肝纤维化后，分别通过尾静脉注射生理盐水（模型组）与10 μg/g 紫杉醇（紫杉醇处理组），另取 10 只正常大鼠以相同的方式注射生理盐水作为对照组。每天注射 1 次，28 d 后处死大鼠获取血与肝组织标本，行肝组织病理学观察，检测血清肝功能生化指标与血清及肝组织胶原相关指标、肝组织 α-SMA、TGF-β1 表达，分离肝星状细胞（HSC），检测 HSC中 TGF-β/Smad 信号通路相关分子的蛋白及 mRNA 的表达。
结果：与对照组比较，模型组出现明显的肝纤维化改变、血清转氨酶水平明显升高，而白蛋白水平明显降低、血清与肝组织胶原相关指标明显升高、肝组织 α-SMA 与 TGF-β1 表达率明显升高、HSC 中TGF-β/Smad 信号通路相关分子的蛋白及 mRNA 明显上调（均 P<0.05）。紫杉醇处理组以上指标的变化程度均明显小于模型组（均 P<0.05），且部分指标与对照组无明显差异（部分 P>0.05）。
结论：紫杉醇对 BSA 诱导大鼠免疫性肝纤维化有抑制作用，机制可能与其抑制 TGF-β/Smad 信号传导通路活化有关。
Inhibitory effect of paclitaxel on hepatic fibrosis induced by bovine serum albumin in rats and its mechanism
CorrespondingAuthor:BIAN Hongzheng Email: 3166001899@qq.com
Abstract
Objective: To investigate the inhibitory eff ect of paclitaxel on hepatic fi brosis induced by bovine serum albumin (BSA) in rats and its mechanism.
Methods: Wistar rats after the formation of immunological liver fibrosis induced by BSA, were injected with normal saline (model group) or 10 μg/g paclitaxel (paclitaxel treatment group) via tail vein respectively, and another 10 normal rats administered with normal saline with the same fashion were served as control group. Injection was performed once daily, and the rats were sacrifi ced and their blood samples and liver specimens were obtained 28 d later, and then histopathological observations were performed, the serum biochemical parameters for liver function and the collagen-related variables in the serum and liver tissue, and the expressions of α-SMA and TGF-β1 in the liver tissue were measured; the hepatic stellate cells (HSCs) were isolated, and then the protein and mRNA expressions of molecules related to TGF-β/Smad signaling pathway in them were determined.
Results: In model group compared with control group, significant liver fibrosis was present, the levels of serum transaminases were significantly increased with significantly decreased albumin level, the collagen-related variables in the serum and liver tissue were significantly augmented, the expression rates of α-SMA and TGF-β1 in the liver tissue were significantly elevated, and the protein and mRNA expressions of molecules related to TGF-β/Smad signaling pathway in the HSCs were significantly up-regulated (all P<0.05). The changing amplitudes of all above variables in paclitaxel treatment group were significantly lower than those in model group (all P<0.05), and some of them showed no significant differences with control group (partial P<0.05).
Conclusion: Paclitaxel has inhibitory effect on immunological liver fibrosis induced by BSA in rats, and the mechanism may probably associated with its suppressing the activity of the TGF-β/Smad signaling pathway.
Keywords：
Liver Cirrhosis; Paclitaxel; Transforming Growth Factor β; Disease Models
Animal
Rats
Methods: Wistar rats after the formation of immunological liver fibrosis induced by BSA, were injected with normal saline (model group) or 10 μg/g paclitaxel (paclitaxel treatment group) via tail vein respectively, and another 10 normal rats administered with normal saline with the same fashion were served as control group. Injection was performed once daily, and the rats were sacrifi ced and their blood samples and liver specimens were obtained 28 d later, and then histopathological observations were performed, the serum biochemical parameters for liver function and the collagen-related variables in the serum and liver tissue, and the expressions of α-SMA and TGF-β1 in the liver tissue were measured; the hepatic stellate cells (HSCs) were isolated, and then the protein and mRNA expressions of molecules related to TGF-β/Smad signaling pathway in them were determined.
Results: In model group compared with control group, significant liver fibrosis was present, the levels of serum transaminases were significantly increased with significantly decreased albumin level, the collagen-related variables in the serum and liver tissue were significantly augmented, the expression rates of α-SMA and TGF-β1 in the liver tissue were significantly elevated, and the protein and mRNA expressions of molecules related to TGF-β/Smad signaling pathway in the HSCs were significantly up-regulated (all P<0.05). The changing amplitudes of all above variables in paclitaxel treatment group were significantly lower than those in model group (all P<0.05), and some of them showed no significant differences with control group (partial P<0.05).
Conclusion: Paclitaxel has inhibitory effect on immunological liver fibrosis induced by BSA in rats, and the mechanism may probably associated with its suppressing the activity of the TGF-β/Smad signaling pathway.