ObjectiveTo observe the curative effect of clinically equivalent doses of Xuesaitong and ginaton injections on cerebral ischemia reperfusion (I/R) injury of rats. MethodsMale rats were randomly divided into five groups: normal control group, sham-operation group, model control group, Xuesaitong group and ginaton group. The cerebral ischemia rat model was established by middle cerebral artery occlusion (MCAO). Rats in the Xuesaitong group were given 20 mg·kg-1 of Xuesaitong injection, and rats in the ginaton group were intravenously injected with 7.5 mg·kg-1 of ginaton immediately after I/R injury and once daily for 7 days. Rats in the sham-operation group and model control group were given the same volume of 0.9% sodium chloride solution. The score of ethology, volume of cerebral infarction, mortality, superoxide dismutase (SOD), malondialdehyde (MDA), xanthine oxidase (XOD), nitrogen oxide (NO) and NO synthase (NOS) in serum were examined. ResultsCompared with model control group, Xuesaitong and ginaton effectively reduced behavioral score 96 h (P<0.05), 120 h (P<0.01), 144 h (P<0.01) and 168 h (P<0.01) after I/R injury, the volume of cerebral infarction 168 h after I/R injury and NO content (P<0.05). But they had no effects on NOS, SOD, MDA, and XOD contents. ConclusionCuratively injecting Xuesaitong and ginaton can effectively reduce cerebral I/R injury, but no significant difference in curative efficacy is observed between Xuesaitong and ginaton at clinically equivalent doses.
表4
5组大鼠脑缺血-再灌注损伤168 h后血清NO,NOS,XOD,SOD和MDA检测值
Tab.4
Serum levels of NO, NOS, XOD, SOD and MDA 168 h after cerebral ischemia reperfusion in five groups of rats x¯±s
组别
剂量/ (mg·kg-1)
大鼠/只
NO (μmol/L)
NOS
XOD
SOD
MDA/ (nmol·mL-1)
(U·mL-1)
空白对照组
-
5
18.70±10.70
17.20±4.73
20.40±1.57
352.0±57.6
11.50±2.64
假手术组
-
5
24.70±9.12
15.50±3.40
24.10±3.19
306.0±21.2
11.80±1.45
模型对照组
-
8
34.80±15.80
21.20±3.59*1
35.30±3.48
306.0±34.5
13.10±2.33
血塞通组
20
7
14.90±7.77*2
18.70±4.11
40.10±11.10
285.0±18.9
13.30±2.62
金纳多组
7.5
7
17.60±5.76*2
20.50±4.81
31.90±10.80
272.0±13.8
11.70±1.66
Compared with shame operation group, *1P<0.01; Compared with model control group, *2P<0.05
与假手术组比较,*1P<0.05;与模型对照组比较,*2P<0.05
表4
5组大鼠脑缺血-再灌注损伤168 h后血清NO,NOS,XOD,SOD和MDA检测值
Tab.4
Serum levels of NO, NOS, XOD, SOD and MDA 168 h after cerebral ischemia reperfusion in five groups of rats x¯±s
NO 是由NOS催化L-精氨酸生成[10]。脑缺血-再灌注损伤后,NO过度生成,体内生成大量的羟自由基(OH-)和二氧化氮(NO2),从而介导神经毒性作用[11]。本实验研究发现,血塞通、金纳多均可降低大鼠血清NO的含量,减少由于过多NO释放对脑的损伤。抑制NO的释放可能是这2种药物治疗脑缺血-再灌注损伤共存的机制。
WU PF,ZHANGZ,WANGF,et al.Natural compounds from traditional medicinal herbs in the treatment of cerebral ischemia /reperfusion injury[J].Acta Pharmacologica Sinica,2010,31(12):1523-1531.
ABSTRACT More and more attention in the field of drug discovery has been focused on the neuroprotection of natural compounds from traditional medicinal herbs. Cerebral ischemia is a complex pathological process involving a series of mechanisms, and a framework for the development of neuroprotectants from traditional herb medicine is a promising treatment for cerebral ischemia. Natural compounds with the effects of anti-oxidation, anti-inflammation, calcium antagonization, anti-apoptosis, and neurofunctional regulation exhibit preventive or therapeutic effects on experimental ischemic brain injury. According to the pharmacological mechanisms underlying neuroprotection, we evaluated natural products from traditional medicinal herbs that exhibit protective effects on ischemic brain injury and characterized the promising targets.
LONGA ZE,WEINSTEIN ER,CARLSONS,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stoke,1989,20(1):84-92.
To develop a simple, relatively noninvasive small-animal model of reversible regional cerebral ischemia, we tested various methods of inducing infarction in the territory of the right middle cerebral artery (MCA) by extracranial vascular occlusion in rats. In preliminary studies, 60 rats were anesthetized with ketamine and different combinations of vessels were occluded; blood pressure and arterial blood gases were monitored. Neurologic deficit, mortality rate, gross pathology, and in some instances, electroencephalogram and histochemical staining results were evaluated in all surviving rats. The principal procedure consisted of introducing a 4-0 nylon intraluminal suture into the cervical internal carotid artery (ICA) and advancing it intracranially to block blood flow into the MCA; collateral blood flow was reduced by interrupting all branches of the external carotid artery (ECA) and all extracranial branches of the ICA. In some groups of rats, bilateral vertebral or contralateral carotid artery occlusion was also performed. India ink perfusion studies in 20 rats documented blockage of MCA blood flow in 14 rats subjected to permanent occlusion and the restoration of blood flow to the MCA territory in six rats after withdrawal of the suture from the ICA. The best method of MCA occlusion was then selected for further confirmatory studies, including histologic examination, in five additional groups of rats anesthetized with halothane. Seven of eight rats that underwent permanent occlusion of the MCA had resolving moderately severe neurologic deficits (Grade 2 of 4) and unilateral infarcts averaging 37.6 +/- 5.5% of the coronal sectional area at 72 hours after the onset of occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
LUNDY EF,SOLIK BS,FRANK RS,et al.Morphometriceval uation of brain infarcts in rats and gerbils[J]. J Pharmacol Methods,1986,16( 3):201-214.
ABSTRACT The Levine rat preparation, the gerbil stroke model, and appropriate control animals were used to determine if the 2,3,5-triphenyltetrazolium chloride (TTC) would selectively identify noninfarcted versus infarcted cerebral tissue. The TTC is frequently used to quantify infarcted myocardial tissue and has been shown to have great specificity, reproducibility, and efficacy. The TTC produces a red product upon reaction with the respiratory enzymes (dehydrogenases) present in non-infarcted tissues. Irreversibly damaged tissues, lacking dehydrogenases, do not form red reaction products. Six gerbil brains and seven rat brains were incubated with the TTC, and the unreacted areas were macroscopically identified. The brains were fixed and sectioned for routine hematoxylin and eosin staining to determine the specificity of the TTC. The TTC was found to react selectively only with non-infarcted cerebral tissue. The gross brain sections were evaluated by macroscopic morphometric analysis, and the unreacted area was always ipsilateral to ligation and correlated with histologic identification of infarct. The brains from neurologically intact animals demonstrated neither macroscopic nor histological evidence of infarction. This technique allows macroscopic quantification of infarct size by planimetry. The average area of infarct for the neurologically impaired rats was 34.7% and it was 31.4% for the impaired gerbils. The percentage of surface area of each infarcted slice was found to correlate with the severity of the neurologic deficit. We conclude that TTC staining is effective for macroscopically delineating cerebral infarcts in rats and gerbils, thus permitting quantification of infarct size.
IKEDAY, LONG DM.The molecular basis of brain injury and brain edema the role of oxygen free radicals[J].Neurosurgery,1990,27(1):1-11.
This review article outlines basic concepts and pathophysiological aspects of the chemistry of oxygen free radicals in all forms of brain injury and brain edema. Recent experimental studies have demonstrated that oxygen free radicals may be important mediators of brain injury and brain edema, and pharmacological antagonism of oxygen free radicals shows beneficial therapeutic results. A number of fundamental questions need to resolved, and advanced techniques for detecting oxygen free radicals will be needed. No clinical data are available, but oxygen free radical scavengers may possibly become a critical therapeutic modality for brain injury and brain edema.
... NO 是由NOS催化L-精氨酸生成[10].脑缺血-再灌注损伤后,NO过度生成,体内生成大量的羟自由基(OH-)和二氧化氮(NO2),从而介导神经毒性作用[11].本实验研究发现,血塞通、金纳多均可降低大鼠血清NO的含量,减少由于过多NO释放对脑的损伤.抑制NO的释放可能是这2种药物治疗脑缺血-再灌注损伤共存的机制. ...
中药单体对脑缺血-再灌注损伤保护的实验研究进展
1
2012
... NO 是由NOS催化L-精氨酸生成[10].脑缺血-再灌注损伤后,NO过度生成,体内生成大量的羟自由基(OH-)和二氧化氮(NO2),从而介导神经毒性作用[11].本实验研究发现,血塞通、金纳多均可降低大鼠血清NO的含量,减少由于过多NO释放对脑的损伤.抑制NO的释放可能是这2种药物治疗脑缺血-再灌注损伤共存的机制. ...
, 李钊飞, 王钢, 陈琼芳, 杨秀芬
