目的 觀察經脂多糖（LPS）誘導后連續(xù)給予何首烏醇提液（AEP）7 d大鼠的肝損傷程度及膽汁淤積相關指標的變化。方法 將雄性SD大鼠隨機分為5組：對照組、LPS組、LPS+對乙酰氨基酚（APAP）組、AEP組、LPS+AEP組，LPS、LPS+APAP、LPS+AEP組按大鼠體質量分別尾iv給予4 mg/kg LPS，對照組與AEP組給予等體積生理鹽水；2 h后LPS+APAP組ig給予625 mg/kg APAP，AEP組與LPS+AEP組ig給予12 g/kg，每天1次，連續(xù)給藥7 d，建立特異質肝損傷炎癥模型。觀察體質量變化，并分別于造模后2 h、14 h、5 d、8 d檢測血清生化中肝功能相關指標的變化，同時收集膽汁，計算膽汁流速與密度，并檢測膽汁中主要成分變化。進行肝臟系數及組織病理學檢查，并對膽汁淤積相關蛋白膽鹽輸出泵轉運蛋白（BSEP）、多藥耐藥蛋白2（MRP2）及多藥耐藥蛋白3（MRP3）進行Real-Time PCR檢測。結果 經過LPS誘導2 d后，LPS+AEP組與對照組、AEP組比較體質量明顯下降，5、8 d肝臟系數顯著增加（P＜0.05）；血清生化指標分析結果顯示，與對照組比較，LPS+AEP組丙氨酸氨基轉移酶（ALT）、天門冬氨酸氨基轉移酶（AST）水平無明顯變化；造模后8 d的總膽紅素（TBIL）明顯降低（P＜0.05），ALP明顯升高（P＜0.05）；可觀察到膽汁密度和膽汁流速明顯降低（P＜0.05），對膽汁成分分析顯示，與對照組比較，LPS+AEP組總膽固醇（TCHO）顯著升高、TBIL顯著降低（P＜0.05）；病理結果顯示，AEP組出現輕微肝細胞變性，而LPS+AEP組可見嚴重局灶壞死；轉錄水平結果發(fā)現，LPS誘導后可使得BSEP、MRP2在14 h時出現短期抑制（P＜0.05），單獨給予AEP可使BSEP、MRP2和MRP3的表達水平短時顯著升高（P＜0.05、0.01），而LPS+AEP給藥第8 d對大鼠肝臟BSEP、MRP2無顯著性影響，可使MRP3轉錄水平升高（P＜0.05）。結論 經LPS誘導的AEP可明顯損傷大鼠肝細胞并干擾膽汁分泌功能，引起膽汁成分相關生化指標的改變，對BSEP與MRP2水平無顯著影響，MRP3出現代償性升高，提示確實存在膽汁淤積癥狀，但可能是存在其他機制。

Objective To observe the rats with liver damage induced by lipopolysaccharide (LPS) after administration of alcohol extract of Polygonum multiflorum (AEP) for 7 d, and study the change of related indicators of cholestasis. Methods Male SD rats were randomly divided into five groups: control group, LPS group, LPS + acetaminophen (APAP) group, AEP group, and LPS+AEP group. A dosage of 4 mg/kg LPS was injected to the caudal vein of rats in the LPS and the LPS+AEP groups. Two hours later, rats wereig administered with AEP (12 g/kg, equivalent to 22 times the dose of clinical medication) respectively for 7 d, once daily. Since the liver-injury model of inflammation was successfully established, the general conditions of rats such as body weight and clinical observation were observed. Liver function-related indicators were detected and bile was collected to determine flow rate, density and changes of major compositions 2 h, 14 h, 5 d, and 8 d after modeling. After getting the organ to body weight ratio for each rat, liver samples were treated for histopathological observation and the mRNA expression of hepatic BSEP, MRP2, and MRP3 was detected by real-time PCR. Results Compared with the rats in control group and AEP group, rats treated with LPS+AEP performed weight losing 2 d after modeling, and organ to body weight ratio was significantly increased on day 5 and 8. The results of liver function-related indicators showed that LPS+AEP did not change the contents of ALT and AST in serum, but increased the content of ALP (P< 0.05) and decreased the content of TBIL in serum (P< 0.05). The bile flow and density were decreased by LPS+AEP, while bile composition was obviously changed, the content of TCHO was increased and the content of TBIL was decreased (P< 0.05). Histopathological examination showed that a small amount of hepatocyte degeneration in AEP group was observed, but livers were damaged and grown necrosis partially in the LPS+AEP group. After 14 h, mRNA expression of BSEP and MRP2 in LPS group showed transitory inhibition, but AEP group had a significant up-regulation of mRNA expression of BSEP, MRP2, and MRP3 (P< 0.05). The following two time points, compared with the control group, mRNA expression of BSEP and MRP2 appeared no obvious change in LPS+AEP group, while mRNA expression of MRP3 was significantly increased on day 8 (P< 0.05). Conclusion AEP induced by LPS performs obvious hepatocyte damage, showed a certain effect on expression of bile acid synthesis and changed bile compositions and liver function-related indicators. The mRNA expression of BSEP and MRP2 was not changed significantly, while mRNA expression of MRP3 is compensatory increased, suggesting that cholestatic symptoms exist, but there may be other mechanisms.

重大新藥創(chuàng)制科技重大專項（2013ZX09302303）；重大新藥創(chuàng)制科技重大專項（2012ZX09301003-001-008）；北京市科委基金項目（Z131100006513010）