动物造模 z-bio 2022-06-17 325

　　Objective To study the effect of different dosage regimens of cisplatin on steroid hormone synthesis and reserve function in mice.

　　Methods Forty female ICR mice were divided into 4 groups, cisplatin continuous and interval modeling groups and two control groups. The cisplatin continuous modeling group was administered with 3 mg/kg cisplatin every day for 7 days; the interval modeling group was injected with 10 mg/kg cisplatin once a week, a total of 4 times. Before the last modeling, open field test, rotarod fatigue test and grip test were performed; the body weight was weighed before sacrifice the next day, and the heart, spleen, thymus and bilateral kidneys of mice were harvested and weighed; RT-qPCR was used to detect GnRH and CRH, pituitary Pomc, Fshb, Lhb, Pou1f1 gene expression, and adrenal and ovarian steroid synthase (StAR, Cyp11a1, Cyp21a1, Cyp17a1, Cyp11b1, Hsd3b2, Cyp19a1, Hsd17b1) and receptor (Esr1, Esr2 and Gper1) gene expression; Western Blot detection of StAR, CYP11A1, CYP21A2 and CYP11B1 protein expression in adrenal gland and ovary.

　　Results Compared with the control group: (1) Different frequencies of cisplatin modeling can inhibit the weight gain of mice, and the accumulation of cisplatin can induce the symptoms of Qi deficiency in mice and inhibit the quality of organs. (2) Different frequency of cisplatin modeling can accelerate the activation of primordial follicle differentiation, produce a large number of atretic follicles, induce apoptosis of theca cells and granulosa cells, and reduce healthy mature follicles; but it has little effect on adrenal tissue and cell morphology. (3) The expression of StAR protein in adrenal gland was down-regulated after continuous modeling; StAR increased after interval modeling, but the protein expression of CYP11B1 was down-regulated. (4) After continuous modeling, ovarian Cyp11a1, Hsd3b2, Esr1 and Gper1 gene expressions were up-regulated, and Star and Cyp17a1 gene expressions were down-regulated; StAR protein expression and Hsd3b2 gene expression were down-regulated after interval modeling. (5) The expression of GnRH and CRH genes in hypothalamus was significantly down-regulated after cisplatin continuous modeling. (6) The expression of Pomc, Fshb and Pou1f1 genes in pituitary increased after cisplatin continuous modeling, while the expression of Lhb decreased in interval modeling group.

　　Conclusion Cisplatin can induce the related manifestations of Qi deficiency and Essence Qi deficiency in mice; the ovaries that synthesize steroid hormones are selectively damaged more than the adrenal glands, and short-term continuous administration further inhibits the functions of the HPA axis and HPG axis in the higher central hypothalamus and pituitary gland.