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目的观察自噬基因Beclin-1、凋亡基因Bcl-2、Bax在慢性氟中毒大鼠肾脏中的表达变化,探讨Beclin-1、Bcl-2、Bax在氟中毒肾脏损害过程中的作用。方法将SD大鼠24只随机分为3组,每组8只,对照组(饮用含氟量<0.5 mg/L自来水),低、高氟组(自来水含氟量分别为50、100 mg/L);饲养9个月后,观察大鼠氟斑牙发生情况;氟离子电极法测定尿氟、骨氟含量;显微镜下观察大鼠肾组织病理形态学变化;采用免疫组织化学方法检测大鼠肾组织中Beclin-1、Bcl-2、Bax表达量;用原位杂交法测定大鼠肾脏Beclin-1 mRNA含量。结果低氟组大鼠氟斑牙检出率为75%,高氟组为100%;与对照组比较,低、高氟组大鼠尿氟和骨氟含量分别为[(10.09±0.88)、(18.09±0.89)mg/L和(5 500.84±1 093.47)、(7 477.94±1 315.88)μg/g]明显升高,差异有统计学意义(P<0.05);染氟大鼠肾脏肾小管上皮细胞水肿、间质血管扩张充血,且随染氟剂量增加损伤改变逐渐加重;与对照组比较,低、高氟组大鼠肾组织中Beclin-1、Bax表达[分别为(168.90±8.68)、(146.32±10.02)和(153.74±10.56)、(134.29±9.85)]明显降低(均P<0.05);与对照组比较,低、高氟组大鼠肾组织中Bcl-2表达[分别为(167.64±7.51)、(185.32±8.55)]明显升高(P<0.05);与对照组比较,低、高氟组大鼠肾组织中Beclin-1 mRNA表达[分别为(166.94±13.21)、(146.11±17.66)]明显降低(P<0.05)。结论慢性氟中毒可诱导肾小管上皮细胞自噬和凋亡相关分子的异常表达,自噬和凋亡可能共同参与慢性氟中毒肾脏损伤过程。
Objective To investigate the expression changes of autophagy gene Beclin-1 and Bcl-2 and Bax in the kidney of chronic fluorosis rats and to explore the role of Beclin-1, Bcl-2 and Bax in renal damage induced by fluorosis. Methods Twenty-four Sprague-Dawley rats were randomly divided into 3 groups with 8 rats in each group. The control group (drinking water containing less than 0.5 mg / L tap water), low and high fluoride groups (50 and 100 mg / L). After 9 months of feeding, the incidence of dental fluorosis in rats was observed. The contents of urinary fluoride and bone fluoride in fluoride were measured by fluoride ion electrode method. The pathological changes of renal tissue were observed under microscope. Immunohistochemistry The expression of Beclin-1, Bcl-2 and Bax in renal tissue was detected by immunohistochemical method. The content of Beclin-1 mRNA in rat kidney was determined by in situ hybridization. Results The detection rate of dental fluorosis was 75% in low-fluoride group and 100% in high-fluoride group. Compared with the control group, the urinary fluorine and bone fluorine in low- and high-fluoride group were [(10.09 ± 0.88) (18.09 ± 0.89) mg / L and (5 500.84 ± 1 093.47), (7 477.94 ± 1 315.88) μg / g], the difference was statistically significant (P <0.05) Epithelial cell edema and interstitial vascular dilatation and congestion, and the injury changes gradually with the increase of fluoride dose. Compared with the control group, the expressions of Beclin-1 and Bax in renal tissues of low and high fluoride groups [(168.90 ± 8.68, , (146.32 ± 10.02) and (153.74 ± 10.56), (134.29 ± 9.85)], respectively (all P <0.05). Compared with the control group, the expression of Bcl- (167.64 ± 7.51) and (185.32 ± 8.55)], respectively (P <0.05). Compared with the control group, the expression of Beclin-1 mRNA in renal tissues of low and high fluoride groups [(166.94 ± 13.21, (146.11 ± 17.66)] was significantly lower (P <0.05). Conclusion Chronic fluorosis can induce the abnormal expression of autophagy and apoptosis-related molecules in renal tubular epithelial cells, and autophagy and apoptosis may participate in the process of renal damage induced by chronic fluorosis.