CAJ | 학술논문

目的：观察齐墩果酸对矽肺大鼠肿瘤坏死因子α（ TNF－α）和胶原表达的影响及其可能作用机制。方法：80只SPF级Wistar雄性大鼠，随机分为对照组、模型组、齐墩果酸组和溶剂组，每组20只。除对照组外，其余组大鼠采用非暴露法气管内一次性注入SiO2悬液（250 mg／kg）复制动物矽肺模型。齐墩果酸组自注射SiO2后每天给予齐墩果酸60 mg／kg灌胃，溶剂组每天用0．6％羧甲基纤维素钠溶液（10 mL／kg）灌胃，对照组用生理盐水（10 mL／kg）灌胃，连续56 d。动物分别在注射SiO2后第7、14、28和56天处死（每次每组5只）。处死后检测各组大鼠肺系数，并观察形态学变化；应用ELISA法检测大鼠血清中TNF－α的含量；试剂盒检测肺组织中总胶原蛋白含量；免疫组织化学法检测肺组织核因子κB（NF－κB）表达。结果：（1）与对照组比较，模型组和溶剂组大鼠肺系数和总胶原蛋白含量明显升高，结合形态学变化，矽肺模型造模成功。齐墩果酸组各时点肺系数和总胶原蛋白含量比模型组和溶剂组相应时点低，但比对照组高。（2）模型组和溶剂组大鼠血清中的TNF－α含量各时点明显升高，高峰在第14天，之后稍降，但明显高于对照组，差异有统计学意义；模型组与溶剂组各时点比较，差异无统计学意义。齐墩果酸组TNF－α含量与模型组相比均降低，各时点比较差异有统计学意义。（3）模型组和溶剂组大鼠肺组织中NF－κB表达量逐渐升高，至第28天达高峰，各时点与对照组比较差异均有统计学意义。齐墩果酸组的NF－κB阳性表达趋势与模型组相同，但明显低于模型组而高于对照组，各时点与对照组比较差异有统计学意义。结论：齐墩果酸通过抑制TNF－α和胶原表达减缓矽肺纤维化的发生，可能与NF－κB通路有关。
목적：관찰제돈과산대석폐대서종류배사인자α（ TNF－α）화효원표체적영향급기가능작용궤제。방법：80지SPF급Wistar웅성대서，수궤분위대조조、모형조、제돈과산조화용제조，매조20지。제대조조외，기여조대서채용비폭로법기관내일차성주입SiO2현액（250 mg／kg）복제동물석폐모형。제돈과산조자주사SiO2후매천급여제돈과산60 mg／kg관위，용제조매천용0．6％최갑기섬유소납용액（10 mL／kg）관위，대조조용생리염수（10 mL／kg）관위，련속56 d。동물분별재주사SiO2후제7、14、28화56천처사（매차매조5지）。처사후검측각조대서폐계수，병관찰형태학변화；응용ELISA법검측대서혈청중TNF－α적함량；시제합검측폐조직중총효원단백함량；면역조직화학법검측폐조직핵인자κB（NF－κB）표체。결과：（1）여대조조비교，모형조화용제조대서폐계수화총효원단백함량명현승고，결합형태학변화，석폐모형조모성공。제돈과산조각시점폐계수화총효원단백함량비모형조화용제조상응시점저，단비대조조고。（2）모형조화용제조대서혈청중적TNF－α함량각시점명현승고，고봉재제14천，지후초강，단명현고우대조조，차이유통계학의의；모형조여용제조각시점비교，차이무통계학의의。제돈과산조TNF－α함량여모형조상비균강저，각시점비교차이유통계학의의。（3）모형조화용제조대서폐조직중NF－κB표체량축점승고，지제28천체고봉，각시점여대조조비교차이균유통계학의의。제돈과산조적NF－κB양성표체추세여모형조상동，단명현저우모형조이고우대조조，각시점여대조조비교차이유통계학의의。결론：제돈과산통과억제TNF－α화효원표체감완석폐섬유화적발생，가능여NF－κB통로유관。
[ ABSTRACT] AIM:To observe the effect of oleanolic acid ( OA) on the expression of Tumor necrosis factor-α( TNF-α) and collagen in silicotic rats in vivo and its possible mechanism.METHODS:Male Wistar rats were divided in-to 4 groups according to the randomized block design:control group, model group, OA group and solvent control group (20 rats in each group) .Except control group, the rats in other groups were induced by intratracheal instillation of silicon di-oxide (SiO2;250 mg/kg).The rats in OA group were intragastrically administered with OA (60 mg/kg) from the second day of giving SiO2 .The rats in solvent control group were gavaged daily with 0.6%sodium carboxymethyl cellulose solution (10 mL/kg).The rats in control group were given normal saline under the same condition for 56 consecutive days.All rats were killed at the 7th, 14th, 28th and 56th days.The lung coefficient was detected and the morphological changes were ob-served.The serum contents of TNF-αwere detected by ELISA.The content of total collagen in the lung tissue was meas-ured.The protein level of nuclear factor-κB ( NF-κB) in the lung tissue was determined by immunohistochemical method. RESULTS:(1) According to the morphological changes, the silicosis model was successfully established.Compared with control group, the lung coefficient and total collagen increased obviously in model group and solvent control group.The lung coefficient and total collagen content in OA group at each time point reduced compared with those in model group and sol- <br> vent group, and increased compared with those in control group at the corresponding time points.(2) The serum contents of TNF-αin model group and solvent control group significantly increased, peaking at the 14th day, slightly decreasing af-terward, and showing statistically significant difference at each time point compared with those in control group.No signifi-cant difference between model group and solvent group at different time points was observed.OA had inhibitory effect on the contents of TNF-αcompared with model group and solvent group at the corresponding time points.(3) NF-κB in model group and solvent control group significantly increased, peaking at the 28th day, and showing statistically significant differ-ence at each time point compared with those in control group.The NF-κB expression in OA group was similar to model group, but significantly decreased compared with control group at each time point.CONCLUSION: OA inhibits the ex-pression of TNF-αand collagen and attenuates the silicosis fibrosis, which may be related to the NF-κB pathway.