1.Vasodilatory effect of midazolam on pre-contractions of in-vitro porcine coronary artery and its mechanisms
Junjie REN ; Keke WANG ; Huiyu XU ; Tingjuan HUANG ; Yi LYU ; Dongmei WU ; Xuanping ZHANG ; Xiaojun ZHENG
Chinese Pharmacological Bulletin 2017;33(8):1131-1135
Aim To investigate the effects of midazolam on porcine isolated coronary artery rings pre-contracted by potassium chloride(KCl)and the possible mechanism.Methods The vessel tension recorder system was used.Isotonic tension of porcine isolated coronary artery rings precontracted by KCl(30 mmol·L-1)was recorded.The vasorelaxing action of midazolam and effects of various drugs were observed in the rings.Results Midazolam(3×10-6~1×10-4 mol·L-1)respectively concentration-dependently reduced the contraction induced by KCl,and there was significant difference between the rings with intact and denude endothelium(P<0.05).On KCl-induced precontraction,midazolam′s relaxation was depressed by L-NAME and the blend of L-NAME and L-Arg(P<0.05),but was not affected by Indo,L-Arg and 1400W.The contraction was not prevented by pretreatment with the inhibitor of Na+/Ca2+ exchanger(KB-R7943).The inhibitor of KATP(Gli)restrained the diastolic function of midazolam(P<0.05),while the inhibitor of BKCa(TEA),Kir(BaCl2),KV(4-AP)had no obvious effect.Conclusions Midazolam produces remarkable vasodilatation on KCl pre-contracted porcine isolated coronary artery rings.Its relaxtion effect is via concentration-dependent and endothelium-dependent mechanisms and relevant to the production of NO.Na+/Ca2+ exchanger is not involved midazolam′s vasodilatation on KCl pre-contracted porcine coronary artery rings.The relaxant mechanism of midazolam may be concerned with KATP.The Kir,BKCa and KV may be not involved.
2.Clinical and molecular genetic analysis of one MODY2 family caused by novel glucokinase gene mutation
Tingjuan ZHENG ; Tong ZHANG ; Yuhuan WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):1032-1036
[Objective] To report a Chinese family with maturity-onset diabetes of the young, type 2 (MODY2) caused by a novel glucokinase (GCK) gene mutation and to analyze its genetic and clinical characteristics. [Methods] Gene sequencing, clinical data collection and analysis were performed on a MODY2 family. [Results] A total of 18 members of this family were investigated, of whom 11 were diabetic, including the proband and her younger brother, father, uncle, cousin and other paternal members. The proband and her brother, father and uncle all had heterosense mutations of GCK gene (exon1: c.45G>A: p.K15K). Bioinformatics function prediction suggested that the mutation might affect mRNA splicing and lead to impaired GCK function. The mutation has not been reported in research on domestic population. The glycosylated hemoglobin levels of the proband and her younger brother were 6.49% and 6.72%; their fasting blood glucose levels were 6.80 mmol/L and 7.01 mmol/L, respectively. The diabetes autoantibody profiles were negative. Blood glucose levels remained stable during 6-18 months of follow-up. [Conclusion] The heterosense mutation of GCK gene in the MODY-2 family (exon1: c.45G>A: p.K15K) is a newly discovered mutation site in the Chinese population, and its clinical manifestations are mild, persistent and stable fasting hyperglycemia, and elevated glycosylated hemoglobin. The pathogenicity of GCK gene synonymous mutations should not be underestimated.