目的 觀察芒果苷單鈉鹽對高膽固醇血癥大鼠肝脂質(zhì)代謝及前蛋白轉(zhuǎn)化酶枯草溶菌素9(PCSK9)/低密度脂蛋白受體(LDLR)的作用。方法 選取SD大鼠40只,將其按體質(zhì)量隨機(jī)分為對照組、模型組、阿托伐他汀鈣片組、芒果苷單鈉鹽組,每組10只。除對照組外,其余各組采用高脂飼料喂養(yǎng)法建立高膽固醇血癥模型。造模成功后,阿托伐他汀鈣片組ig阿托伐他汀鈣片5 mg/kg,芒果苷單鈉鹽組ig 80 mg/kg芒果苷單鈉鹽,給藥8周后,觀察各組體質(zhì)量及肝臟指數(shù)變化,生化法檢測各組血脂指標(biāo)[三酰甘油(TG)、總膽固醇(TC)、高密度脂蛋白膽固醇(HDL-C)、低密度脂蛋白膽固醇(LDL-C)],腎功能、血清酶指標(biāo)[肌酐(CRE)、血清尿素(UREA)、肌酸激酶(CK)、乳酸脫氫酶(LDH)]及肝組織游離膽固醇(FC)、總膽汁酸(TBA)的含量,蘇木精-伊紅染色(HE)觀察大鼠肝組織形態(tài)學(xué)變化,RT-PCR檢測肝組織中白細(xì)胞介素-1β(IL-1β)和CD68 mRNA表達(dá),Western blotting及RT-PCR檢測肝組織中PCSK9、LDLR的蛋白及mRNA表達(dá)。結(jié)果 與模型組相比,各給藥組大鼠體質(zhì)量和肝臟指數(shù)明顯降低(P<0.05);血清中TC、LDL-C及CRE、UREA、CK、LDH水平顯著降低,HDL-C水平顯著升高(P<0.05);肝組織中FC含量降低,TBA含量升高(P<0.05);肝臟脂肪變性改善明顯;肝組織I L-1β、CD68 mRNA表達(dá)明顯減少(P<0.05),同時顯著降低了PCSK9的蛋白和mRNA水平,提升了LDLR的蛋白和mRNA水平(P<0.05)。結(jié)論 芒果苷單鈉鹽可有效調(diào)節(jié)高膽固醇血癥大鼠肝膽固醇代謝,減輕高脂造成的心腎功能損害,其作用可能與調(diào)節(jié)肝臟PCSK9/LDLR信號通路的表達(dá),改善脂質(zhì)代謝紊亂相關(guān)。

Objective To observe the effects of mangiferin monosodium salt on hepatic lipid metabolism and PCSK9/LDLR in hypercholesterolemic rats. Methods Forty SD rats were selected and randomly divided into 4 groups according to their body mass:control group, model group, Atorvastatin Calcium Tablets group, and mangiferin monosodium salt group, with 10 rats in each group. In addition to the control group, the other groups were fed with high-fat diet to establish hypercholesterolemia model. After the establishment of the model, the Atorvastatin Calcium Tablets group was ig Atorvastatin Calcium Tablets 5 mg/kg, mangiferin group was ig mangiferin 80 mg/kg, mangiferin monosodium salt group was ig 80 mg/kg mangiferin monosodium salt, respectively. After 8 weeks of administration, observe the changes of body mass and liver index in each group. Detect the four items of blood lipids (TC, TG, LDL-C, HDL-C) in serum, renal function, serum enzyme indexes (CRE, UREA, CK, LDH), and the contents of FC and TBA in liver tissue by biochemical method. HE staining was used to observe the morphological changes of rat liver. The mRNA expression of IL-1β and CD68 in liver tissue were detected by RT-PCR. Western blotting and RT-PCR were used to detect the protein and mRNA expression of PCSK9 and LDLR in liver tissues. Results Compared with the model group, the body mass and liver index of rats in each group were significantly decreased (P < 0.05). The levels of TC, LDL-C, CRE, UREA, CK, LDH in serum were significantly decreased, but HDL-C was increased (P < 0.05). The content of FC in liver tissue was decreased, and the content of TBA was increased (P < 0.05). The liver steatosis was significantly improved. mRNA Expression of IL-1β in liver tissue was significantly increased, and CD68 was significantly decreased (P < 0.05). The protein and mRNA level of PCSK9 was significantly decreased, and the levels of LDLR was increased (P < 0.05). Conclusion Mangiferin monosodium salt can effectively regulate the liver cholesterol metabolism in hypercholesterolemic rats and reduce the damage of heart and kidney function caused by hyperlipidemia, which may be related to regulating the expression of PCSK9/LDLR signal pathway in the liver and improving the disorder of lipid metabolism.

R285.5

河北省中醫(yī)藥管理局中醫(yī)藥類科研計劃項目(2022615)