目的 探討半夏瀉心湯促進(jìn)胃腸動(dòng)力的物質(zhì)基礎(chǔ)、作用機(jī)制和配伍特點(diǎn)。方法 將實(shí)驗(yàn)分為半夏瀉心湯組及苦降藥組,兩組大鼠分別ig 給予兩組藥物水提醇沉液,于給藥前(0 h)及給藥后0.083、0.167、0.25、0.333、0.5、0.75、1、1.5、2、3、4、6、9、24 h 股靜脈采血,ELISA 法測Cajal 間質(zhì)細(xì)胞(ICC)中KIT 蛋白、Ca²⁺及ATP 酶的水平,同時(shí)采用液質(zhì)聯(lián)用(HPLC-MS)法檢測血清中黃芩苷、黃芩素、小檗堿、巴馬汀的濃度,采用Winnonlin 軟件進(jìn)行藥動(dòng)學(xué)(PK)- 藥效學(xué)(PD)結(jié)合模型擬合。結(jié)果 半夏瀉心湯及其苦降藥組均能下調(diào)ICC 中Ca²⁺濃度及上調(diào)ICC 中ATP 酶的水平;且對ICC 內(nèi)KIT 蛋白水平無顯著影響。半夏瀉心湯及其苦降藥組降低Ca²⁺濃度的效應(yīng)中巴馬汀以有滯后時(shí)間三房室-Sigmoid I_maxPK-PD模型連接,小檗堿、黃芩素以有滯后時(shí)間二房室-Sigmoid I_max PK-PD 模型連接。半夏瀉心湯及其苦降藥組上調(diào)ATP 酶的效應(yīng)中巴馬汀以有滯后時(shí)間三房室-Sigmoid E_max PK-PD 模型連接,小檗堿、黃芩素以有滯后時(shí)間二房室-Sigmoid E_max PK-PD模型連接。結(jié)論 半夏瀉心湯及其苦降藥組促進(jìn)胃腸動(dòng)力的作用可能與其降低ICC 內(nèi)Ca²⁺濃度、上調(diào)細(xì)胞ATP 酶水平有關(guān)。ICC 內(nèi)Ca²⁺濃度的降低、ATP 酶水平的上調(diào)可能與半夏瀉心湯及其苦降藥組中巴馬汀、小檗堿、黃芩素有關(guān)。半夏瀉心湯在PK 和PD 方面均優(yōu)于苦降藥組,體現(xiàn)出全方的配伍優(yōu)勢。

Objective To investigate the material basis, mechanism, and compatibility characteristics of Banxia Xiexin Decoction (BXD) in promoting the gastrointestinal motility. Methods The rats were divided into BXD group and bitter medicine group. Blood samples were collected before administration (0 h) and 0.083, 0.167, 0.25, 0.333, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 24 h after administration by venous blood collection. ELISA method was used to detect the changes of KIT protein content, Ca²⁺ concentration, and ATP enzyme level at different time points in BXD group and bitter medicine group. HPLC-MS method was established for simultaneous determination of baicalin, baicalein, berberine, and palmatine in rat plasma. Winnonlin software was used to fit PK-PD model. Results In BXD and bitter medicine groups, the Ca²⁺ concentration was decreased and the ATP enzyme level was increased in ICC. BXD and bitter medicine containing serum had no significant effect on KIT protein. By fitting the berberine, baicalin, and palmatine of BXD group with Ca²⁺ concentration, to identify palmatine was connected to effect room with lag time three compartment-Sigmoid I_max PK-PD model. Berberine, baicalin were connected with lag time two compartment-Sigmoid I_max PK-PD model. By fitting the berberine, baicalin, palmatine of BXD group with ATP enzyme, to identify palmatine was connected to effect room with lag time three compartment-Sigmoid E_max PK-PD model. Berberine, baicalin were connected with lag time two compartment- Sigmoid E_max PK-PD model. Conclusion BXD and bitter medicine group in promoting gastrointestinal function may be related to the reduction of Ca²⁺concentration and upregulation of ATP enzyme in ICC. The decreasing of Ca²⁺ concentration and increasing of ATP enzyme level may be related to berberine, baicalin, and palmatine in BXD and its bitter medicine. PK and PD in BXD are superior to the bitter medicine group, which shows the advantages of full compatibility.