Effects of Zishui Qinggan Lichong Granule on neurotransmitter disorder in EMs mice induced by GnRHa*
2019, 42 (9):
Objective To observe the effects of Zishui Qinggan Lichong Granule (ZQLG) (Water-nourishing, Liver-heat-clearing and Chong mai-regulating Granule) on monoamine neurotransmitter in brain tissue of mice with endometriosis (EMs) induced by gonadotropin releasing hormone agonist (GnRHa) and to verify its safety by monitoring the immunological factors in eutopic and ectopic endometrial tissues. Methods BALB/c mice were randomly divided into normal group, model group, GnRHa group, high-dose ZQLG group, mid-dose ZQLG group and low-dose ZQLG group. Except for the normal group, endometrial fragments of donated mice were injected intraperitoneally into the abdominal cavity of mice in other groups to establish the mouse model of endometriosis. Except for the normal group and the model group, GnRHa (1.4 mg/kg) was injected once subcutaneously to the other groups since the 21st day after the model establishment. From the day of subcutaneous injection of GnRHa, the high-, mid- and low-dose ZQLG groups began to receive Zishui Qinggan Lichong Granule by gavage [48, 24, 12 g/kg] for 30 days, and the normal group, model group and GnRHa group were given the same volume of saline by gavage. After the intervention, the content of 5-HT, NE and DA in brain tissue of mice in each group was detected by ELISA, and the expression of TNF-α, IL-1, MMP-2 and TIMP-2 was detected by immunohistochemistry. Results The contents of 5-HT, NE and DA in brain tissue after GnRHa injection were lower than those in the model group. The contents of 5-HT in brain tissue increased after ZQLG intervention in the low-, mid- and high-dose ZQLG groups(P<0.05). The contents of NE and DA in brain tissue increased in the mid- and high-dose ZQLG groups(P<0.05). Compared with model group, the expressions of TNF-α, IL-1 and MMP-2 in eutopic and ectopic endometrial tissues decreased and expression of TIMP-2 increased after GnRHa injection. There was no increase in TNF-α, IL-1, MMP-2 expressions or decrease in TIMP-2 expressions in any ZQLG group after intervention. Conclusion GnRHat led to a decline in the contents of such monoamine neurotransmitters as 5-HT, NE, and DA in mice brain tissue. However, Zishui Qinggan Lichong Granule can effectively increase the levels of such monoamine neurotransmitters in mice brain tissue and relieve perimenopausal neurotransmitter disorders caused by GnRHa. At the same time, it does not cause immune dysfunction in endometriosisits, delivering satisfying safety.
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