ABSTRACT
Our previous study showed that H3 receptor antagonists reduced neuronal apoptosis and cerebral infarction in the acute stage after cerebral ischemia, but through an action independent of activation of histaminergic neurons. Because enhanced angiogenesis facilitates neurogenesis and neurological recovery after ischemic stroke, we herein investigated whether antagonism of H3R promoted angiogenesis after brain ischemia. Photothrombotic stroke was induced in mice. We showed that administration of H3R antagonist thioperamide (THIO, 10 mg·kg-1·d-1, i.p., from D1 after cerebral ischemia) significantly improved angiogenesis assessed on D14, and attenuated neurological defects on D28 after cerebral ischemia. Compared with wild-type mice, Hrh3-/- mice displayed more blood vessels in the ischemic boundary zone on D14, and THIO administration did not promote angiogenesis in these knockout mice. THIO-promoted angiogenesis in mice was reversed by i.c.v. injection of H3R agonist immepip, but not by H1 and H2 receptor antagonists, histidine decarboxylase inhibitor α-fluoromethylhistidine, or histidine decarboxylase gene knockout (HDC-/-), suggesting that THIO-promoted angiogenesis was independent of activation of histaminergic neurons. In vascular endothelial cells (bEnd.3), THIO (10-9-10-7 M) dose-dependently facilitated cell migration and tube formation after oxygen glucose deprivation (OGD), and H3R knockdown caused similar effects. We further revealed that H3R antagonism reduced the interaction between H3R and Annexin A2, while knockdown of Annexin A2 abrogated THIO-promoted angiogenesis in bEnd.3 cells after OGD. Annexin A2-overexpressing mice displayed more blood vessels in the ischemic boundary zone, which was reversed by i.c.v. injection of immepip. In conclusion, this study demonstrates that H3R antagonism promotes angiogenesis after cerebral ischemia, which is independent of activation of histaminergic neurons, but related to the H3R on vascular endothelial cells and its interaction with Annexin A2. Thus, H3R antagonists might be promising drug candidates to improve angiogenesis and neurological recovery after ischemic stroke.
Subject(s)
Annexin A2 , Brain Ischemia , Ischemic Stroke , Receptors, Histamine H3 , Animals , Mice , Histidine Decarboxylase/genetics , Histidine Decarboxylase/metabolism , Receptors, Histamine H3/metabolism , Histamine , Endothelial Cells/metabolism , Brain Ischemia/drug therapy , Mice, Knockout , Cerebral InfarctionABSTRACT
OBJECTIVE: To discuss the effects of C-E-CKC and CKC in treating precancerous lesions of the cervix(CIN2,CIN3)and its influence on fertility preservation.METHODS: Select 138 patients who accepted conization of cervix with CIN2,CIN3 from January 2013 to January 2017 in our hospital,the C-E-CKC group consisted of 81 cases and the CKC group 57 cases.Compare the average operation time,the average intraoperative blood loss,cone length,the preoperative and postoperative pathological coincidence rates,the positive rate of the tangent margin,the rate of the recurrence rate,postoperative complications rate,and the pregnancy situation and outcome of two groups.RESULTS: The average operation time of C-E-CKC and CKC group was(29.60±5.98)min and(33.67±5.95)min,respectively,and the average intraoperative blood loss was(14.01±12.00)mL and(19.56±16.10)mL.In C-E-CKC group,the conical excision length of type I,Ⅱ and Ⅲ transformation zone was(1.56±0.18)cm,(1.58±0.24)cm and(1.67±0.29)cm,while in CKC group,it was(1.71 ±0.34)cm,(1.80±0.37)cm and(2.20±0.27)cm,and the differences between the groups were statistically significant(P0.05).CONCLUSION: The two methods are both safe and effective for treating precancerous lesions of the cervix(CIN2,CIN3).C-E-CKC is with shorter operation time,less intraoperative bleeding and smaller excision of cervical tissue,and the damage to cervix is smaller,which is more suitable for patients to preserve fertility.
