The Relationship Study Between Vascular Reactivity And BKca Channel In Vascular Smooth Muscle Of Type2 Diabetes Mellitus Rat

Abstract: Objective: This study accord to the correlation researchs at present in international,especially aim at the status that the lack of research data about the relationship between vascular reactivity and potassium channels in T2DM rats. Use low dose STZ and high fat food to copy the T2DM rat model similar to the clinical appearance,and use vascular ring testing technique,the research object are thoracic aorta and mesentery small vascular , systematically research the relationship between big,small vascular reactivity and activity changes of BKca channel in T2DM rats.Try to reveal the internal association between vascular reactivity and BKca channe in smooth muscle in T2DM rats from integer,organ level,in order to reveal the Electrophysiology changes of BKca channe,chaneel gene and the channel expression changes,and the regulatory mechanism in smooth muscle in T2DM rats from cell,molecule level. Methods: (1)The establishment of type2 diabete mellitus rat model:SD rat is feeded with high-fat and high-glucose food a moth, and then inject STZ to the abdominal cavity by the dose of 2mg/kg one time. (the STZ was maded to 0.25% level by 0.1mol/L citric acid buffer solution , which PH is 4.2).Get the vena caudalis blood from rats at the state of empty stomach to measure blood glucose,and choose the rats which empty stomach blood glucose≥7.0 as the successful diabete mellitus model. (2) The mesenteric artery was quickly detached in solutionâ… , the free artery was cut into vascular rings (0.3⁰.4 cm). Vascular rings were suspended with two silver wires and fixed in a 37℃chamber with 95%O2 and 5%CO2. Vascular rings were linked to electro-physiolograph with tension transducer and biological amplifier. Use Chart software to collect data and analysis data. Observe the relax reaction of vascular circle after using the IBTX. KCl was used to test activity of vascular rings and cause contraction. Results:(1)The index of successful type2 diabete mellitus rat model: the weight of model group(n=10)rat began significantly reducing from the eighth week to the twelveth week ,which are 238±27g,244±27g,228±30g,and compared with normal control group (n=10)which are 316±22g,326±23g,334±28g,the difference is significan(tP<0.01). when get the sample,measure the blood glucose,systolic blood pressure,diastolic blood pressure in model group,which are 16.95±2.57mmol/L,145±28 mmHg,118±24 mmHg;and compared with normal control group (n=10)which are 6.7±053 mmHg,102±9 mmHg,80±9 mmHg,blood glucose,systolic blood pressure,diastolic blood pressure of model group significantly increase,the difference is significant(P<0.01). The index of insulin,insulin sensitive index and lipid(LDL-C,TG,TC) in rat plasma of model group(n=8),which are 115.53±75.18μIU/ml,0.0006±0.0003,1.16±0.12 mmol/L,1.97±0.13 mmol/L,4.22±0.23 mmol/L,compared with the normal control group(n=8),which are 16.23±6.03μIU/ml,1.01±0.11 mmol/L,0.82±0.09 mmol/L,2.53±0.15 mmol/L,insulin and lipid in rat plasma of model group significantly increase,the difference is significan(tP<0.01). (2)Changes of vascular relax reaction caused by SNP after adding IBTX in mesenteric artery vascular ring: the accumulative relaxation percentage of rat mesenteric artery vascular ring after adding IBTX in model group(10^-7,10^-6,10^-5μmmol/L SNP), which are 29±6,40±8,52±6, compared with before adding IBTX, which are 57±9,79±7,84±6, the accumulative relaxation percentage of model group significantly decrease after adding IBTX, the difference is significant(P<0.01). the accumulative relaxation percentage of rat mesenteric artery vascular ring after adding IBTX in normal control group (10^-7,10^-6,10^-5μmmol/L SNP),which are 35±9,63±5,75±12,compared with before adding IBTX, which are 46±14,71±9,81±12, the accumulative relaxation percentage of model group also decrease after adding IBTX,there is not significant difference(P>0.05).(3)Changes of vascular relax reaction caused by SNP after adding IBTX in thoracic aorta vascular ring: the accumulative relaxation percentage of rat thoracic aorta vascular ring after adding IBTX in model group(10^-7,10^-6,10^-5μmmol/L SNP), which are 4±3,18±6,17±5, compared with before adding IBTX, which are 9±4,26±5,29±6, the accumulative relaxation percentage of model group significantly decrease after adding IBTX, the difference is significant(P<0.01). the accumulative relaxation percentage of rat thoracic aorta vascular ring after adding IBTX in normal control group (10^-7,10^-6,10^-5μmmol/L SNP),which are 6±2,37±5,40±6,compared with before adding IBTX, which are 11±7,44±9,51±14, the accumulative relaxation percentage of model group also decrease after adding IBTX,there is not significant difference(P>0.05).Conclusion:1 The copy of model is successful,it has feature of high blood glucose,hypertension,high Lip and insulin resistance. 2 vascular relax reaction caused by KCl in rat vascular ring in model group compared with normal group,there is not significant difference;and vascular contractile response caused by PE in rat vascular ring in model group strengthed. 3 the accumulative relaxation percentage of rat vascular smooth muscle after adding IBTX in model group decreased,but the accumulative relaxation percentage of rat vascular smooth muscle after adding IBTX in normal group doesn't obviously change. The finding indicates that the increase of openning ratio of BKca channel.