CAJ | 학술논문

目的：观察柴胡人参药对对非酒精性脂肪性肝病（ NAFLD）大鼠法尼醇X受体（ FXR）蛋白和固醇调节元件结合蛋白（ SREBP-1c）表达及胰岛素抵抗的影响。方法：雄性Wistar大鼠喂养高脂高糖饲料，造模8周后随机分为模型对照组（ M）、西药组（ R）和柴胡人参药对组（ Y），分别给予生理盐水、罗格列酮和药对灌胃治疗4周，同时继予高脂高糖饲料喂养。检测大鼠空腹血糖（FBG）、血脂、血清丙氨酸氨基转移酶（ALT）和天冬氨酸转氨酶（AST）、胰岛素（FINS）水平并计算胰岛素抵抗指数（IRI）；取肝脏，计算肝重指数，检测肝组织甘油三酯（TG）水平；做肝脏HE染色，光镜下观察肝脂肪变性和炎症程度。用Western blot检测肝组织的FXR及SREBP-1c蛋白表达水平，用实时荧光定量PCR （Real-time PCR）检测FXR mRNA的表达情况。结果： Y组大鼠血清TC、 TG、 LDL-C、FBG、 FINS、 IRI水平较M组显著降低（P＜0.05或P＜0.01）， HDL-C水平未见明显变化（P＞0.05）。光镜下观察见Y组大鼠肝脏脂肪病变较M组明显减轻，而R组脂肪变性改善程度不明显。 Western blot 检测结果显示：与M组比较， Y组大鼠肝脏FXR蛋白表达显著升高（ P＜0.01）， SREBP-1c蛋白表达显著降低（ P＜0.05）； Real-time PCR检测结果显示：与M组比较， Y组大鼠肝脏FXR mRNA表达显著升高（ P＜0.01）。结论：柴胡人参药对能够改善NAFLD大鼠肝脏脂肪变和炎症程度，激活FXR的活性，间接抑制SREBP-1c的蛋白表达，从而降低NAFLD大鼠血清TC、 TG、 LDL-C和肝脏TG含量，改善胰岛素抵抗，这可能是其治疗NAFLD的机制之一。
목적：관찰시호인삼약대대비주정성지방성간병（ NAFLD）대서법니순X수체（ FXR）단백화고순조절원건결합단백（ SREBP-1c）표체급이도소저항적영향。방법：웅성Wistar대서위양고지고당사료，조모8주후수궤분위모형대조조（ M）、서약조（ R）화시호인삼약대조（ Y），분별급여생리염수、라격렬동화약대관위치료4주，동시계여고지고당사료위양。검측대서공복혈당（FBG）、혈지、혈청병안산안기전이매（ALT）화천동안산전안매（AST）、이도소（FINS）수평병계산이도소저항지수（IRI）；취간장，계산간중지수，검측간조직감유삼지（TG）수평；주간장HE염색，광경하관찰간지방변성화염증정도。용Western blot검측간조직적FXR급SREBP-1c단백표체수평，용실시형광정량PCR （Real-time PCR）검측FXR mRNA적표체정황。결과： Y조대서혈청TC、 TG、 LDL-C、FBG、 FINS、 IRI수평교M조현저강저（P＜0.05혹P＜0.01）， HDL-C수평미견명현변화（P＞0.05）。광경하관찰견Y조대서간장지방병변교M조명현감경，이R조지방변성개선정도불명현。 Western blot 검측결과현시：여M조비교， Y조대서간장FXR단백표체현저승고（ P＜0.01）， SREBP-1c단백표체현저강저（ P＜0.05）； Real-time PCR검측결과현시：여M조비교， Y조대서간장FXR mRNA표체현저승고（ P＜0.01）。결론：시호인삼약대능구개선NAFLD대서간장지방변화염증정도，격활FXR적활성，간접억제SREBP-1c적단백표체，종이강저NAFLD대서혈청TC、 TG、 LDL-C화간장TG함량，개선이도소저항，저가능시기치료NAFLD적궤제지일。
Objective: To investigate the effects of the drug pair of ginseng and Radix bupleuri on the expression of the pro-tein of FXR (farnesoid x receptor) and SREBP-1c (sterol regulatory element binding protein lc ) and insulin resistance in rats with NAFLD.Methods: Forty-four male rats were randomly divided into 4 groups: blank control group ( C, n=10 ) , model control group (M, n=10), drug pair group (Y, n=10) and rosiglitazone group (R, n=10) .Excluding the blank control group eating standard chow for 12 weeks, the rats were fed with high-fat and high-sugar diet for 8 weeks.The M, Y and R groups were still administered the same diet and given by physiological saline , drug pair and rosiglitazone intragastric treatment 4 weeks, then the levels of fasting blood glucose (FBG), blood-lipoids, fasting insulin (Fins), leptin, AST, ALT were deter-mined and the insulin resistance index ( IRI) and liver index were measured;livers were weighed and collected to be observed for liver histopathologic changes under light microscope.The expression of FXR and SREBP-1c protein were detected by using west-ern blot.The expression of FXR mRNA was analyzed with real-time PCR mRNA quantification.Results: The level of FBG , TC, TG, LDL-C, leptin, Fins, IRI, AST, ALT, and liver index in Y group were lower than M group ( P<0.01, P<0.05) .Liver histopathologic changes were reduced than M group , but the degree of adipohepatic improvement is not obvious in the R group.Western blot analysis showed that the expression of FXR protein was increased and SREBP -1c protein was decreased in Y group compared with the M group ( P<0.05) .Real-time PCR mRNA quantification showed that compared with the M group , expres-sion of FXR mRNA was significantly increased in the Y group ( P<0.01 ) .Conclusion: The drug pair of ginseng and Radix bupleuri can relieve liver injury and inflammation degree , and improve the activity of FXR , and indirect inhibit the expression of the SREBP-1c protein, then reduce the level of TC , TG, LDL-C and improve insulin resistance.This may be one of the mecha-nisms in treatment of NAFLD.