Background:Tetramine(tetramethylene disulphotetramine, TET), commonlyknown called "top mice killer", was a highly toxic rodenticides andresponsible for a great percentage of death and injury. Although TEThas been forbidden in China for many years, illegal production andselling of TET always make the accident poisoning of TET. ZhangChunyin, Zhu Dongjun and some other researchers have demonstratedthat TET was the antagonism of GABA acceptor in animal experiments;and that TET could block the combination of GABA and its acceptor,which leads to the convulsion because of the over-exciting of centralnever system, or even the death due to the respiratory failure. Animalexperiments further show good detoxification of Na-DMPS for acuteTET poisoning animals. Clinical studies also confirm the benefic effectof Na-DMPS. At present, clinical therapies for TET poisoning includegastric lavage, blood purification, controlling convulsion whichadminister valium, luminal, VitB6 and calcium, detoxification ofNa-DMPS. Meanwhile it was the important that the comprehensivemethods which could improve the functions of heart, lung, brain andother organs.Neuron-specific enolase (NSE), the specialty of which lies on neuron and nerve incretion cell, covers 1.5%of total dissolublealbumen in brain. The content of NSE in blood was 30 times lowerthan that in brain at least. S 100 was a kind of acidity calcium combinedalbumen, which mainly exists in astrocyte, and the rise of its levelreflects the damage scale of glial cell. Many researches have manifestedthat the changing concentration of NSE and S100 in cerebrospinalfluid or serum occurred in the cases like cerebrovascular disease,braintrauma,epilepsy,intracranial infection,hepatic encephalopathy,carbonmonoxide toxic encephalopathy. NSE and S100 could indicate thedamage scale of neuron. Therefore, the determination of NSE and S100has a great effect on the diagnosis of nerve system diseases, evaluationof the severity of diseases, prognosis and the guidance to the therapy.QingKaiLing injection was a compound Chinese traditionalmedicine which made from AnGongBezoarPill (Pill for heat-cleatingand detoxicating). That injection, with the function of cleating awaythe heat-evil and expelling superficial evils and refreshment, has beenwidely used not only for the treatment of minor febrile convulsion,coma,acute cerebrovascular disease in adult, hepatic coma and so on,but also for the protection of brain with cerebral arterial thrombosis andintracranial infection. Recent researches have found that QingKaiLinginjection, with the function of anti-nerve-toxicity for glutamic acid, waseffective for the treatment of TET poisoning. That study is going to observe the change of concentration of serum NSE, S100, and theexpression of NSE-mina, S 100-mRNA in brain tissue in TET poisoningrats, and to probe the therapeutic efficacy of QingKaiLing in clinicaltreatment of TET poisoning.Objectives:This research was to observes the effects of QingKaiLing on theconvulsion latent period and convulsion paroxysm period, the change ofserum concentration of NSE, S 100, and the expression of NSE-mRNA,S100-mRNA brain tissue of rat after acute TET poisoning and toexplore the mechanism of QingKaiLing against TET poisoning. Theresults of the research will provide theory foundation for medicineusage during the clinic treatment of TET poisoning.Methods:After making the model of TET poisoning, SD rats were dividedinto TET poisoning, Na-DMPS group, low dose QingKaiLing group(1ml/100g), medium QingKaiLing group(2ml/100g), high QingKaiLinggroup (4ml/100g). The change of behavior of rats were recorded in allgroups. The change of serum concentration of NSE, S100 weredetermined by the method of ELISA in 5 groups, and the expression ofNSE-mRNA, S100-mRNA in brain tissue were assayed with RT-PCR method. Statistics were generated using SPSS (version 11.0) DunnettT test, SKN-q test and Fisher's exact test were applied for the statisticanalysis. We regarded P<0.05.Results:1. The change of behavior: compared with TET poisoning group,The latent period was longer in Na-DMPS group and the grade ofconvulsion was decreased in Na-DMPS group (P<0.05)QingKaiLing groups show same phenomena with dose-related change.Compared with TET poisoning group, medium and high dose groups(2ml/100g, 4ml/100g) were observed with significant difference(P<0.01). there were no significant difference between Na-DMPSgroup and high dose groups (P>0.05).2. The change of NSE and S100 concentration: compared withTET poisoning group, the serum concentration ofNSE, S100 weresignificant decreased in Na-DMPS group and QingKaiLing groups(P<0.01). However, there was significant difference betweenmedium and high QingKaiLing dose groups (2ml/100g, 4ml/100g) andTET poisoning group (P<0.01); while no significant difference wasfound between QingKaiLing groups and Na-DMPS group (P>0.05).3. The change of expression of NSE-mina in brain tissue: In thecerebral cortex of rat, compared with TET poisoning group, the expression of NSE-mRNA of brain tissue was significantly increasedin Na-DMPS group, medium and high dose QingKaiLing groups(2ml/100g, 4ml/100g) (P<0.01), while low dose QingKaiLing group(1ml/100g) shows no significant difference (P>0.05).In the cerebral hippocampus of rat, Compared with TET poisoninggroup, the expression of NSE-mRNA was increased in Na-DMPS groupwith no statistic meaning (P>0.05). the expression of NSE-mRNAexpression was increased in various dose QingKaiLing groups(P<0.01)with dose-related difference.4. The change of expression S100-mRNA of brain tissue:compared with TET poisoning group, the expression of S 100-mRNA inthe cerebral cortex of rat was increased significantly in Na-DMPSgroup, medium and high dose QingKaiLing groups(2ml/100g, 4ml/100g) (P<0.01). and there was no significantdifference between medium and high dose QingKaiLing groups(P>0.05); in the cerebral hippoeampus of rat, compared with TETpoisoning group, the expression of S100-mRNA brain tissue wasincreases significantly in Na-DMPS and medium, high doseQingKaiLing groups (P<0.01).Conclusions:1. The medium and high dose QingKaiLing could prolong the latent period of convulsion for acute TET poisoning rat, and decreased thegrade of convulsion.2. The Medium and high dose QingKaiLing could decrease theconcentration of serum NSE and S100. Depending on its dose,QingKaiLing may protect the brain damage in rat due to acute TETpoisoning, just like Na-DMPS.3. For acute TET poisoning rat, the medium and high QingKaiLingdose increased the expressions of NSE-mRNA in cortex andhippocampus. Depending on its dose, it showed that QingKaiLingincrease NSE content in brain cell, which strengthened the energymetabolize of the damaged brain tissue and reinforce the ATP providing.That was the one part of the brain-protecting mechanism of QingKaiLing.4. For acute TET poisoning rat, the medium and high doseQingKaiLing enhance the expression of S 100-mRNA in cortex of braintissue. Depending on its dose, QingKaiLing may increase the content ofS 100 in brain cell to nurture the damaged brain glial cell, and decreaseconsistence of C a2+ in cell to protect brain tissue. That was another partof the brain-protecting mechanism of QingKaiLing.5. The comparison between QingKaiLing and Na-DMPS the studyshowed that both of them increased the expressions of NSE, S 100 mRNAin cortex brain tissue. But there were some difference in hippocampusbetween them. QingKaiLing could increase the expression of NSE-mRNA significantly, and Na-DMPS increased the expression ofS100-mRNA significantly. |