目的 观察槲皮素对慢性混合反流性食管炎大鼠食管黏膜损伤的保护作用及对核转录因子κB (NF-κB)/白细胞介素(IL)-6信号通路的影响.方法 采用贲门结扎术+食管十二指肠吻合术建立慢性混合反流性食管炎大鼠模型.48只健康清洁级SD雄性大鼠采用随机数字表法分为正常对照组、假手术组、模型对照组、奥美拉唑组、低剂量槲皮素组和高剂量槲皮素组,每组8只,分别腹腔注射生理盐水2 ml(正常对照组、假手术组和模型对照组)、奥美拉唑20 mg/kg(奥美拉唑组)、槲皮素100 mg/kg(低剂量槲皮素组)和槲皮素200 mg/kg(高剂量槲皮素组),每日1次.6周后处死,光镜下观察食管组织的形态学改变并评分,分别采用免疫组织化学染色及酶联免疫吸附试验检测NF-κB p65、IL-6蛋白在大鼠食管黏膜及血清中的表达,各组进行比较.结果 正常对照组、假手术组、模型对照组、奥美拉唑组、低剂量槲皮素组、高剂量槲皮素组大鼠的食管黏膜病理评分分别为0.250±0.463、0.250±0.463、2.625±0.518、1.500±0.535、1.250±0.463、1.375±0.518;食管黏膜NF-κB p65蛋白评分分别为0.500±0.535、0.625±0.518、3.500±0.535、1.875±0.649、1.750±0.707、2.000±0.535;食管黏膜IL-6蛋白评分分别为1.125±0.641、1.125±0.835、5.375±0.518、2.375±0.518、2.000±0.535、2.250±0.463;血清NF-κB p65蛋白含量分别为(68.618±18.500)、(77.824±22.228)、(184.882±49.165)、(106.693±45.312)、(76.215±16.588)、(108.207±42.107) pg/ml;血清IL-6蛋白含量分别为(24.826±4.008)、(23.599±4.351)、(51.378±9.697)、(32.370±11.657)、(23.085±4.660)、(26.243±4.955) pg/ml.假手术组与正常对照组比较,以上5项指标差异均无统计学意义(P=1.000、P=0.642、P=1.000、P=0.518、P=0.673);正常对照组、假手术组、奥美拉唑组、低剂量槲皮素组和高剂量槲皮素组与模型对照组比较,差异均有统计学意义(P <0.001、P<0.001、P<0.001、P=0.002、P=0.001;P<0.001、P<0.001、P<0.001、P =0.004、P=0.002;P=0.001、P<0.001、P<0.001、P=0.025、P=0.023;P均<0.001;P<0.001、P<0.001、P<0.001、P=0.023、P<0.001);低剂量槲皮素组、高剂量槲皮素组与奥美拉唑组比较,差异均无统计学意义(P =0.334、P=0.717、P=0.176、P=0.121、P=0.074;P=0.642、P =0.678、P=0.619、P=0.949、P=0.225);低剂量槲皮素组与高剂量槲皮素组比较,差异均无统计学意义(P =0.619、P=0.438、P=0.334、P=0.086、P=0.243).大鼠食管黏膜病理评分与黏膜NF-κB p65、IL-6蛋白含量呈明显正相关(r=0.803,P<0.001;r=0.758,P<0.001),与血清NF-κB p65、IL-6蛋白含量亦呈明显正相关(r=0.486,P=0.004;r=0.544,P=0.001).结论 大鼠食管黏膜损伤程度越大,黏膜及血清NF-κB p65、IL-6蛋白含量越高.槲皮素能降低反流性食管炎大鼠食管黏膜的损伤程度,其作用机制可能与下调反流性食管炎大鼠NF-κB、IL-6水平,减轻食管炎症有关.
目的 觀察槲皮素對慢性混閤反流性食管炎大鼠食管黏膜損傷的保護作用及對覈轉錄因子κB (NF-κB)/白細胞介素(IL)-6信號通路的影響.方法 採用賁門結扎術+食管十二指腸吻閤術建立慢性混閤反流性食管炎大鼠模型.48隻健康清潔級SD雄性大鼠採用隨機數字錶法分為正常對照組、假手術組、模型對照組、奧美拉唑組、低劑量槲皮素組和高劑量槲皮素組,每組8隻,分彆腹腔註射生理鹽水2 ml(正常對照組、假手術組和模型對照組)、奧美拉唑20 mg/kg(奧美拉唑組)、槲皮素100 mg/kg(低劑量槲皮素組)和槲皮素200 mg/kg(高劑量槲皮素組),每日1次.6週後處死,光鏡下觀察食管組織的形態學改變併評分,分彆採用免疫組織化學染色及酶聯免疫吸附試驗檢測NF-κB p65、IL-6蛋白在大鼠食管黏膜及血清中的錶達,各組進行比較.結果 正常對照組、假手術組、模型對照組、奧美拉唑組、低劑量槲皮素組、高劑量槲皮素組大鼠的食管黏膜病理評分分彆為0.250±0.463、0.250±0.463、2.625±0.518、1.500±0.535、1.250±0.463、1.375±0.518;食管黏膜NF-κB p65蛋白評分分彆為0.500±0.535、0.625±0.518、3.500±0.535、1.875±0.649、1.750±0.707、2.000±0.535;食管黏膜IL-6蛋白評分分彆為1.125±0.641、1.125±0.835、5.375±0.518、2.375±0.518、2.000±0.535、2.250±0.463;血清NF-κB p65蛋白含量分彆為(68.618±18.500)、(77.824±22.228)、(184.882±49.165)、(106.693±45.312)、(76.215±16.588)、(108.207±42.107) pg/ml;血清IL-6蛋白含量分彆為(24.826±4.008)、(23.599±4.351)、(51.378±9.697)、(32.370±11.657)、(23.085±4.660)、(26.243±4.955) pg/ml.假手術組與正常對照組比較,以上5項指標差異均無統計學意義(P=1.000、P=0.642、P=1.000、P=0.518、P=0.673);正常對照組、假手術組、奧美拉唑組、低劑量槲皮素組和高劑量槲皮素組與模型對照組比較,差異均有統計學意義(P <0.001、P<0.001、P<0.001、P=0.002、P=0.001;P<0.001、P<0.001、P<0.001、P =0.004、P=0.002;P=0.001、P<0.001、P<0.001、P=0.025、P=0.023;P均<0.001;P<0.001、P<0.001、P<0.001、P=0.023、P<0.001);低劑量槲皮素組、高劑量槲皮素組與奧美拉唑組比較,差異均無統計學意義(P =0.334、P=0.717、P=0.176、P=0.121、P=0.074;P=0.642、P =0.678、P=0.619、P=0.949、P=0.225);低劑量槲皮素組與高劑量槲皮素組比較,差異均無統計學意義(P =0.619、P=0.438、P=0.334、P=0.086、P=0.243).大鼠食管黏膜病理評分與黏膜NF-κB p65、IL-6蛋白含量呈明顯正相關(r=0.803,P<0.001;r=0.758,P<0.001),與血清NF-κB p65、IL-6蛋白含量亦呈明顯正相關(r=0.486,P=0.004;r=0.544,P=0.001).結論 大鼠食管黏膜損傷程度越大,黏膜及血清NF-κB p65、IL-6蛋白含量越高.槲皮素能降低反流性食管炎大鼠食管黏膜的損傷程度,其作用機製可能與下調反流性食管炎大鼠NF-κB、IL-6水平,減輕食管炎癥有關.
목적 관찰곡피소대만성혼합반류성식관염대서식관점막손상적보호작용급대핵전록인자κB (NF-κB)/백세포개소(IL)-6신호통로적영향.방법 채용분문결찰술+식관십이지장문합술건립만성혼합반류성식관염대서모형.48지건강청길급SD웅성대서채용수궤수자표법분위정상대조조、가수술조、모형대조조、오미랍서조、저제량곡피소조화고제량곡피소조,매조8지,분별복강주사생리염수2 ml(정상대조조、가수술조화모형대조조)、오미랍서20 mg/kg(오미랍서조)、곡피소100 mg/kg(저제량곡피소조)화곡피소200 mg/kg(고제량곡피소조),매일1차.6주후처사,광경하관찰식관조직적형태학개변병평분,분별채용면역조직화학염색급매련면역흡부시험검측NF-κB p65、IL-6단백재대서식관점막급혈청중적표체,각조진행비교.결과 정상대조조、가수술조、모형대조조、오미랍서조、저제량곡피소조、고제량곡피소조대서적식관점막병리평분분별위0.250±0.463、0.250±0.463、2.625±0.518、1.500±0.535、1.250±0.463、1.375±0.518;식관점막NF-κB p65단백평분분별위0.500±0.535、0.625±0.518、3.500±0.535、1.875±0.649、1.750±0.707、2.000±0.535;식관점막IL-6단백평분분별위1.125±0.641、1.125±0.835、5.375±0.518、2.375±0.518、2.000±0.535、2.250±0.463;혈청NF-κB p65단백함량분별위(68.618±18.500)、(77.824±22.228)、(184.882±49.165)、(106.693±45.312)、(76.215±16.588)、(108.207±42.107) pg/ml;혈청IL-6단백함량분별위(24.826±4.008)、(23.599±4.351)、(51.378±9.697)、(32.370±11.657)、(23.085±4.660)、(26.243±4.955) pg/ml.가수술조여정상대조조비교,이상5항지표차이균무통계학의의(P=1.000、P=0.642、P=1.000、P=0.518、P=0.673);정상대조조、가수술조、오미랍서조、저제량곡피소조화고제량곡피소조여모형대조조비교,차이균유통계학의의(P <0.001、P<0.001、P<0.001、P=0.002、P=0.001;P<0.001、P<0.001、P<0.001、P =0.004、P=0.002;P=0.001、P<0.001、P<0.001、P=0.025、P=0.023;P균<0.001;P<0.001、P<0.001、P<0.001、P=0.023、P<0.001);저제량곡피소조、고제량곡피소조여오미랍서조비교,차이균무통계학의의(P =0.334、P=0.717、P=0.176、P=0.121、P=0.074;P=0.642、P =0.678、P=0.619、P=0.949、P=0.225);저제량곡피소조여고제량곡피소조비교,차이균무통계학의의(P =0.619、P=0.438、P=0.334、P=0.086、P=0.243).대서식관점막병리평분여점막NF-κB p65、IL-6단백함량정명현정상관(r=0.803,P<0.001;r=0.758,P<0.001),여혈청NF-κB p65、IL-6단백함량역정명현정상관(r=0.486,P=0.004;r=0.544,P=0.001).결론 대서식관점막손상정도월대,점막급혈청NF-κB p65、IL-6단백함량월고.곡피소능강저반류성식관염대서식관점막적손상정도,기작용궤제가능여하조반류성식관염대서NF-κB、IL-6수평,감경식관염증유관.
Objective To observe the protective effects of quercetin on esophageal mucosa in chronic mixed reflux esophagitis (RE) rats and the effect of quercetin on nuclear factor (NF)-κB/interleukin (IL)-6 signaling pathway.Methods Mixed RE model was successfully induced by cardia ligation and esophagoduodenostomy.48 healthy male Sprague-Dawley rats were equally divided into the following 6 groups using random number table method:normal control group,sham-operation group,model control group,omeprazole group,low-dose quercetin group,and high-dose quercetin group.The 6 groups were treated with peritoneal injection of 2 ml normal saline (normal control,sham-operation,model control groups),20 mg/kg omeprazole,100 mg/kg quercetin (low-dose) and 200 mg/kg quercetin (high-dose) once daily,respectively.The rats were sacrificed after 6 weeks of intervention.The microscopic pathological changes of esophageal mucosa were scored.NF-κB p65 and IL-6 protein levels in esophageal mucosa and serum were assessed using immunohistochemistry and enzyme-linked immunosorbent assay,respectively.Results In normal control group,shamoperation group,model control group,omeprazole group,low-dose quercetin group and high-dose quercetin group,the pathological scores of esophageal mucosa were 0.250 ± 0.463,0.250 ± 0.463,2.625 ± 0.518,1.500 ±0.535,1.250 ±0.463,and 1.375 ±0.518; the NF-κB p65 protein scores in esophageal mucosa were 0.500±0.535,0.625 ±0.518,3.500 ±0.535,1.875 ±0.649,1.750 ±0.707,and 2.000 ±0.535; the IL-6 protein scores in esophageal mucosa were 1.125 ± 0.641,1.125 ± 0.835,5.375 ± 0.518,2.375 ± 0.518,2.000 ±0.535,and 2.250 ±0.463; the serum NF-κB p65 protein levels were (68.618 ± 18.500),(77.824 ± 22.228),(184.882 ± 49.165),(106.693 ± 45.312),(76.215 ± 16.588),and (108.207 ± 42.107) pg/ml; the serum IL-6 protein levels were (24.826 ±4.008),(23.599 ±4.351),(51.378 ± 9.697),(32.370 ± 11.657),(23.085 ± 4.660),and (26.243 ± 4.955) pg/ml.In terms of the 5 indicators,there were no statistically significant differences between the normal control group and the sham-operation group (P =1.000,P =0.642,P =1.000,P =0.518,P =0.673) ; the results in the normal control,shamoperation,omeprazole,low-dose quercetin,and high-dose quercetin groups were significantly different from those in the model control group (P < 0.001,P < 0.001,P < 0.001,P =0.002,P =0.001 ; P < 0.001,P < 0.001,P<0.001,P=0.004,P=0.002; P=0.001,P<0.001,P<0.001,P=0.025,P=0.023; all P <0.001 ; P <0.001,P <0.001,P <0.001,P =0.023,P <0.001) ; there were no statistically significant differences between low-dose quercetin group and omeprazole group,nor between high-dose quercetin group and omeprazole group (P=0.334,P=0.717,P=0.176,P=0.121,P =0.074; P =0.642,P=0.678,P=0.619,P =0.949,P =0.225); there were no statistically significant differences between low-dose quercetin group and high-dose quercetin group (P =0.619,P =0.438,P =0.334,P =0.086,P =0.243).The microscopic pathological score of esophageal mucosa was positively correlated with NF-κB p65 and IL-6 protein scores in esophageal mucosa (r =0.803,P < 0.001 ; r =0.758,P < 0.001),also positively correlated with serum NF-κB p65 and IL-6 protein levels (r=0.486,P=0.004; r=0.544,P=0.001).Conclusions The expression levels of NF-κB p65 and IL-6 protein in esophageal mucosa and serum increase with the severity of esophageal mucosal injury.Quercetin can reduce the severity of esophageal mucosal injury in RE,possibly through down-regulating NF-κB and IL-6 expression and mitigatng esophageal inflammatory status.
