芪泽汤抗慢性肾功能衰竭配伍规律及机制研究
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摘要
目的：
选用正交数字表L8(26)对芪泽汤进行拆方并观察各组方药对慢性肾功能衰竭(CRF)大鼠肾组织中转化生长因子-β1(TGF-β1)、血小板反应蛋白-1(TSP-1)表达的影响,探讨芪泽汤及其拆方抗CRF的配伍规律和作用机制,为中医临床治疗CRF遣方用药提供实验参考。方法：
选用正交数字表L8(26),不考虑药物之间的交互作用将芪泽汤拆为8组：全方组、黄芪葛根泽兰组、大黄泽兰组、黄芪大黄益母草组、黄芪牛蒡子组、益母草葛根组、大黄牛蒡子葛根组、牛蒡子益母草泽兰组。将90只雄性SD大鼠随机分为11组,正常组、模型组、尿毒清组、拆方8组,其中模型组10只,余组各8只。除正常组外,其余各组使用腺嘌呤灌胃建立CRF大鼠模型；同时,拆方8组每天灌服对应的芪泽汤及其拆方药物,尿毒清组灌服尿毒清药液,模型组、正常组口服等容量蒸馏水进行干预,连续28天。观察各组大鼠肾脏形态学、肾功能等指标的变化,分析各拆方组药物配伍特点,用免疫组化技术检测各组大鼠肾组织TGF-β1、TSP-1蛋白的表达。
结果：
①各组大鼠体重变化：模型组、大黄泽兰组、大黄牛蒡子葛根组、牛蒡子益母草泽兰组大鼠体重在前3周随时间延长而增长,第4周出现下降,以模型组下降最为明显。其余各组大鼠体重均随时间延长而增长。
②肾功能变化：与模型组比较,尿毒清组、全方组、黄芪葛根泽兰组、黄芪大黄益母草组、益母草葛根组的大鼠BUN、Scr明显下降(P<0.05),肾功能有所改善。
③肾组织病理形态学变化：与模型组比较,除黄芪牛蒡子组外,其余药物干预组大鼠肾重、肾脏指数均有明显降低(P<0.05)肾小球肾小管病理损伤积分结果表明,模型组肾脏病理损伤最严重,药物干预组均较模型组明显减轻(P<0.01),其中以全方组、尿毒清组肾组织病理改善最为明显。
④肾组织TGF-β1、TSP-1表达：正常组大鼠肾组织中几乎没有TSP-1表达,TGF-β1有微量表达；模型组大鼠肾组织内TGF-β1、TSP-1存在高表达；与模型组比较,除大黄牛蒡子葛根组外,其他各用药干预组大鼠肾组织中TGF-β1、TSP-1表达明显下降有显著差异(P<0.01),其中以尿毒清组、全方组、黄芪葛根泽兰组、黄芪大黄益母草组表达最低。
结论：
芪泽汤全方组、黄芪葛根泽兰组、黄芪大黄益母草组对腺嘌呤致CRF模型大鼠的肾功能有较好的保护作用,可减轻肾组织病理损害,减缓CRF的发展。补气药配伍活血利水药是改善CRF的有效药物配伍。减少CRF模型大鼠肾组织中TGF-β1、TSP-1的表达,从而改善肾间质纤维化,可能是芪泽汤能够减缓CRF发展的重要机制。
Objective:
To investigate the compatible regulation of Qize decoction by observing the effects of Qize decoction and its disassembled compositions on resisting chronic renal failure.To discover the effective combination from the Qize decoction and its disassembled compositions. To explore the mechanism of resisting chronic renal failure of the effective combination and provide the experimental reference for the clinical.
Methods:
Choosing the digital form L8 (26) of orthogonal design which ignoring the interaction of the different herbs, the Qize decoction was disassembled into 8 groups: the whole prescription, the Huangqi-Gegen-Zelan group, the Dahuang-Zelan group, the Huangqi-Dahuang-Yimucao group, the Huangqi-Niubangzi group, the Yimucao-Gegen group, the Dahuang-Niubangzi-Gegen group, the Niubangzi-Yimucao-Zelan group.90 male Sprague Dawley(SD)rats were randomly divided into eleven groups:the blank control group(8 rats),the model group(10 rats),the Niaoduqing group(8 rats) and the eight disassembled groups(8 rats every group). Every rat was treated with 2% adenine in the morning and stomached its group correspondence decoction in the afternoon for 28 days except the blank control group. Common physical change of the 11 groups rats were observed. Blood urea nitrogen (BUN) and serum creatinine (Scr) of those were detected. Pathological change of the experimental rats'renal tissue were observed by Hematoxylin and eosin staining (HE) method. The protein expression of transforming growth factor-β1 (TGF-β1) and Thrombospondin-1(TSP-1) in the experimental rats'renal tissue were examined by immunohistochemistry.
Results:
①The change of weight in every group:The rats'weight in the model group, the Dahuang-Zelan group,the Dahuang-Niubangzi-Gegen group and the Niubangzi-Yimucao-Zelan group increased with the time in the first three weeks, and began to decline in the fourth week, especially the model group. On the other side, the rats'weight in the rest groups increased with the time during the four weeks.
②The change of kidney function:Compared with the model group, the level of BUN, Scr in the Niaoduqing group, the whole prescription group, the Huangqi-Gegen-Zelan group, the Huangqi-Dahuang-Yimucao group and the Yimucao-Zelan group were lower (P<0.05).
③The renal histomorphological change in every group:Compared with the model group, the kidney weight, renal index in the rest groups decreased significantly (P<0.05) except the Huangqi-Niubangzi group. Compared with the model group, the pathological damage in the other groups were lighter (P<0.01), especially in the whole prescription group and the Niaoduqing group.
④The protein expression of TGF-β1, TSP-1:There were little TSP-1 protein expression and low TGF-β1 protein expression in renal tissue in the blank control group, while high protein expression of TGF-β1 and TSP-1 in the model group. Compared with the model group, the protein expression of TGF-β1 and TSP-1 in renal tissue in the rest groups except the Dahuang-Niubangzi-Gegen group were lower (P<0.01), and the protein expression of those in the Niaoduqing group, the whole prescription group, the Huangqi-Gegen-Zelan group and the Huangqi-Dahuang-Yimucao group were lower significantly.
Conclusion:
The whole prescription group, the Huangqi-Gegen-Zelan group and the Huangqi-Dahuang-Yimucao group could protect the renal function of adenine-induced CRF rats, depress the pathological damage and delay the process of CRF. Combination of qi-tonifying herbs, damp-draining diuretic, blood-activating herbs might improve the CRF effectively. The Qize decoction could improve CRF by reducing the protein expression of TGF-β1 and TSP-1 in the renal tissue.
选用正交数字表L8(26)对芪泽汤进行拆方并观察各组方药对慢性肾功能衰竭(CRF)大鼠肾组织中转化生长因子-β1(TGF-β1)、血小板反应蛋白-1(TSP-1)表达的影响,探讨芪泽汤及其拆方抗CRF的配伍规律和作用机制,为中医临床治疗CRF遣方用药提供实验参考。方法：
选用正交数字表L8(26),不考虑药物之间的交互作用将芪泽汤拆为8组：全方组、黄芪葛根泽兰组、大黄泽兰组、黄芪大黄益母草组、黄芪牛蒡子组、益母草葛根组、大黄牛蒡子葛根组、牛蒡子益母草泽兰组。将90只雄性SD大鼠随机分为11组,正常组、模型组、尿毒清组、拆方8组,其中模型组10只,余组各8只。除正常组外,其余各组使用腺嘌呤灌胃建立CRF大鼠模型；同时,拆方8组每天灌服对应的芪泽汤及其拆方药物,尿毒清组灌服尿毒清药液,模型组、正常组口服等容量蒸馏水进行干预,连续28天。观察各组大鼠肾脏形态学、肾功能等指标的变化,分析各拆方组药物配伍特点,用免疫组化技术检测各组大鼠肾组织TGF-β1、TSP-1蛋白的表达。
结果：
①各组大鼠体重变化：模型组、大黄泽兰组、大黄牛蒡子葛根组、牛蒡子益母草泽兰组大鼠体重在前3周随时间延长而增长,第4周出现下降,以模型组下降最为明显。其余各组大鼠体重均随时间延长而增长。
②肾功能变化：与模型组比较,尿毒清组、全方组、黄芪葛根泽兰组、黄芪大黄益母草组、益母草葛根组的大鼠BUN、Scr明显下降(P<0.05),肾功能有所改善。
③肾组织病理形态学变化：与模型组比较,除黄芪牛蒡子组外,其余药物干预组大鼠肾重、肾脏指数均有明显降低(P<0.05)肾小球肾小管病理损伤积分结果表明,模型组肾脏病理损伤最严重,药物干预组均较模型组明显减轻(P<0.01),其中以全方组、尿毒清组肾组织病理改善最为明显。
④肾组织TGF-β1、TSP-1表达：正常组大鼠肾组织中几乎没有TSP-1表达,TGF-β1有微量表达；模型组大鼠肾组织内TGF-β1、TSP-1存在高表达；与模型组比较,除大黄牛蒡子葛根组外,其他各用药干预组大鼠肾组织中TGF-β1、TSP-1表达明显下降有显著差异(P<0.01),其中以尿毒清组、全方组、黄芪葛根泽兰组、黄芪大黄益母草组表达最低。
结论：
芪泽汤全方组、黄芪葛根泽兰组、黄芪大黄益母草组对腺嘌呤致CRF模型大鼠的肾功能有较好的保护作用,可减轻肾组织病理损害,减缓CRF的发展。补气药配伍活血利水药是改善CRF的有效药物配伍。减少CRF模型大鼠肾组织中TGF-β1、TSP-1的表达,从而改善肾间质纤维化,可能是芪泽汤能够减缓CRF发展的重要机制。
Objective:
To investigate the compatible regulation of Qize decoction by observing the effects of Qize decoction and its disassembled compositions on resisting chronic renal failure.To discover the effective combination from the Qize decoction and its disassembled compositions. To explore the mechanism of resisting chronic renal failure of the effective combination and provide the experimental reference for the clinical.
Methods:
Choosing the digital form L8 (26) of orthogonal design which ignoring the interaction of the different herbs, the Qize decoction was disassembled into 8 groups: the whole prescription, the Huangqi-Gegen-Zelan group, the Dahuang-Zelan group, the Huangqi-Dahuang-Yimucao group, the Huangqi-Niubangzi group, the Yimucao-Gegen group, the Dahuang-Niubangzi-Gegen group, the Niubangzi-Yimucao-Zelan group.90 male Sprague Dawley(SD)rats were randomly divided into eleven groups:the blank control group(8 rats),the model group(10 rats),the Niaoduqing group(8 rats) and the eight disassembled groups(8 rats every group). Every rat was treated with 2% adenine in the morning and stomached its group correspondence decoction in the afternoon for 28 days except the blank control group. Common physical change of the 11 groups rats were observed. Blood urea nitrogen (BUN) and serum creatinine (Scr) of those were detected. Pathological change of the experimental rats'renal tissue were observed by Hematoxylin and eosin staining (HE) method. The protein expression of transforming growth factor-β1 (TGF-β1) and Thrombospondin-1(TSP-1) in the experimental rats'renal tissue were examined by immunohistochemistry.
Results:
①The change of weight in every group:The rats'weight in the model group, the Dahuang-Zelan group,the Dahuang-Niubangzi-Gegen group and the Niubangzi-Yimucao-Zelan group increased with the time in the first three weeks, and began to decline in the fourth week, especially the model group. On the other side, the rats'weight in the rest groups increased with the time during the four weeks.
②The change of kidney function:Compared with the model group, the level of BUN, Scr in the Niaoduqing group, the whole prescription group, the Huangqi-Gegen-Zelan group, the Huangqi-Dahuang-Yimucao group and the Yimucao-Zelan group were lower (P<0.05).
③The renal histomorphological change in every group:Compared with the model group, the kidney weight, renal index in the rest groups decreased significantly (P<0.05) except the Huangqi-Niubangzi group. Compared with the model group, the pathological damage in the other groups were lighter (P<0.01), especially in the whole prescription group and the Niaoduqing group.
④The protein expression of TGF-β1, TSP-1:There were little TSP-1 protein expression and low TGF-β1 protein expression in renal tissue in the blank control group, while high protein expression of TGF-β1 and TSP-1 in the model group. Compared with the model group, the protein expression of TGF-β1 and TSP-1 in renal tissue in the rest groups except the Dahuang-Niubangzi-Gegen group were lower (P<0.01), and the protein expression of those in the Niaoduqing group, the whole prescription group, the Huangqi-Gegen-Zelan group and the Huangqi-Dahuang-Yimucao group were lower significantly.
Conclusion:
The whole prescription group, the Huangqi-Gegen-Zelan group and the Huangqi-Dahuang-Yimucao group could protect the renal function of adenine-induced CRF rats, depress the pathological damage and delay the process of CRF. Combination of qi-tonifying herbs, damp-draining diuretic, blood-activating herbs might improve the CRF effectively. The Qize decoction could improve CRF by reducing the protein expression of TGF-β1 and TSP-1 in the renal tissue.
引文
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