目的 研究白芍總苷對大鼠化學(xué)性肝損傷肝陰虛證候模型的影響和作用機(jī)制。方法 SPF級雄性SD大鼠適應(yīng)性喂養(yǎng)后，隨機(jī)分為對照組、模型組、一貫煎組和白芍總苷組。除對照組外，其余各組大鼠ip 20% CCl₄橄欖油溶液，后期ig給予附子、干姜、肉桂溫?zé)嶂兴帍?fù)方制備化學(xué)性肝損傷肝陰虛證模型。一貫煎組、白芍總苷組造模同時(shí)給藥，1次/d，連續(xù)6周。6周后測定大鼠體質(zhì)量、肛溫，觀察其一般狀態(tài)；測定血清丙氨酸轉(zhuǎn)氨酶（ALT）、天冬氨酸轉(zhuǎn)氨酶（AST）、環(huán)磷酸腺苷（cAMP）、環(huán)磷酸鳥苷（cGMP）、6-酮-前列腺素F_1α（6-keto-PGF_1α）、血漿血栓素B₂（TXB₂）、層黏連蛋白（LN）、透明質(zhì)酸（HA）水平及肝組織白細(xì)胞介素-6（IL-6）、IL-10、腫瘤壞死因子-α（TNF-α）水平；檢測肝臟磷脂酰肌醇激酶（PI3k）mRNA、蛋白激酶B（Akt）mRNA和蛋白表達(dá)水平，并取肝臟進(jìn)行HE病理切片檢查。結(jié)果 與模型組比較，白芍總苷組大鼠體征評分有明顯改善（P<0.05），體質(zhì)量顯著升高（P<0.05），血清ALT、AST水平顯著降低（P<0.01、0.001），cAMP/cGMP顯著升高（P<0.01），LN、HA水平均顯著降低（P<0.05、0.001），肝組織TNF-α、IL-6水平顯著降低（P<0.001），Akt蛋白表達(dá)水平顯著降低（P<0.05），PI3K、Akt mRNA表達(dá)水平顯著降低（P<0.05、0.001），同時(shí)肝臟病理損傷有所改善。結(jié)論 白芍總苷具有保護(hù)化學(xué)性肝損傷肝陰虛證的功效，可能是白芍養(yǎng)肝陰的物質(zhì)基礎(chǔ)，其作用機(jī)制可能與抗炎、減輕微循環(huán)障礙、通過抑制PI3K-Akt通路來調(diào)節(jié)細(xì)胞因子IL-6和IL-10平衡有關(guān)。

Objective Based on the establishment of experimental model of liver yin deficiency syndrome, the effects of total glucosides of Paeoniae Radix Alba on the syndrome model of liver yin deficiency syndrome in rats with chemical liver injury were studied. Methods SPF male Sprague-Dawley rats weighing (200±20) g, after adaptive feeding, were randomly divided into control group, model group, Yi Guan Jian group, and total glycosides of Paeoniae Radix Alba group. Except the control group, the rats in the other groups were intraperitoneally injected with 20% CCl₄ olive oil solution, and then ig treated with Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma and Cinnamomi Cortex to establish liver yin deficiency syndrome model. The Yi Guan Jian group and the total glucoside of Paeoniae Radix Alba group were administered at the same time, once a day for 6 weeks. After 6 weeks, the body weight and anal temperature of the rats were measured, and the general state was observed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), 6-keto-prostaglandin F_1α (6-keto-PGF_1α), plasma thrombosis content of B₂ (TXB₂), laminin (LN) and hyaluronic acid (HA) were measured, and the activity of liver tissue interleukin-6 (IL-6), IL-10, and tumor necrosis factor (TNF-α) were measured. The expression levels of phosphatidylinositol kinase (PI3k) mRNA, protein kinase B (Akt) mRNA and protein were determined and livers were taken for pathological examination of HE. Results Compared with the model group, the scores of the total glucosides of Paeoniae Radix Alba group were significantly increased (P<0.05), the body weight was significantly increased (P<0.05), and the serum ALT and AST levels were significantly decreased (P<0.01, 0.001). The cAMP/cGMP ratio was increased significantly (P<0.01). The LN and HA of the liver tissue of the total glycosides group were significantly decreased (P<0.05, 0.001). The content of TNF-α and IL-6 was decreased significantly (P<0.001), the expression level of Akt protein was decreased significantly (P<0.05), the expression of PI3K and Akt mRNA was decreased significantly (P<0.05, 0.001), and liver pathological sections were improved. Conclusion The extract of Paeoniae Radix Alba has the effect of protecting liver injury with yin deficiency syndrome, which may be the material basis of supplement liver yin of Paeoniae Radix Alba. Its mechanism of action may be related to anti-inflammatory, alleviate microcirculatory disorders, and regulate the balance of cytokines IL-6 and IL-10 by inhibiting the PI3K-Akt pathway.

R285.5

國家自然科學(xué)基金資助項(xiàng)目（81673617）；國家中醫(yī)藥管理局中醫(yī)藥行業(yè)科研專項(xiàng)（201507004）