尼卡地平对大鼠Thy1系膜增生性肾小球肾炎的作用及其对肾内Bcl-2/BaX表达的影响

目的：研究尼卡地平诱导系膜细胞调亡在大鼠Thy1系膜增生性肾小球肾炎模型（Thy1模型）中的作用及其与Bcl-2/Bax的表达的关系。方法：（1）应用兔抗大鼠Thy1.1血清建立大鼠Thy1模型；（2）建立模型第7d，腹腔注射尼卡地平（6mg/kg)，以等量生理盐水为对照；（3）应用浸条法测定尿蛋白；（4）应用原位末端标记法检测细胞凋亡；（5）应用免疫组化检测Bcl-2/Bax蛋白的表达。结果：注射尼卡地平组尿蛋白程度明显减轻，恢复较生理盐水组快，常规HE染色显示尼卡地平组肾小球内有核细胞数较生理盐水组少，同时肾小球内凋亡细胞数也增多，尼卡地平组肾小球内Bcl-2蛋白阳性细胞数减少,而Bax蛋白阳性细胞数无明显变化，且Bcl-2阳性细胞数与肾小球内细胞数呈负相关。结论：尼卡地平通过诱导系调亡减轻大鼠Thy1模型的肾小球损害，其机制可能与Bcl-2蛋白表达减少有关。

Effects of NIcardipine on Thy1 Glomerul onephritis and Its Relation With bcl-2/bax gene expression

Objectve: Proliferation of mesangial cells is the most common change in glomerulonephritis.In the past decades,most researches focused on the proliferation of mesangial cells. But apoptosis was very few researched that is another important mechanism to control cell number. Treating Thy1 glomerulonephritis model with nicardipine,which can induce mesangial cell apoptosis in vitro and in vivo.This research is to inquire the effect of nicardipine on Thy1 glomerulonephritis model and its relation with Bcl-2/Bax gene expression.Methods: 1.Thy1 glomerulonephritis model was established using rabbit anti-Thy1 serum injected once in rats. 2. Eight rats of Thy1 model received the following treatment 6mg/kg/day(ip) nicardipine for three days at 7th day,Thy1 model treating with saline as control. 3. Using dipstick method to investigate proteinuria of the animal model.4. Using TUNEL staining to study the apoptosis in glomeruli. 5. Expression of Bcl-2/Bax gene expression in renal tissue cells were measured with Labeled Streptavidin Biotin Assay.Results: Proteinruia were found in rats at 24 hours after injected with anti-Thy1 serum,raised to the highest level at 8th day,almost disappeared at 17th day.The proteinuria level dropped rapidly and disappeared at 96 hours after injected with nicardipine. The number of cells having nucleus per glomerulus cross-section is lower in nicardipine groupthan saline control.We also found that both apoptotic cell and Bcl-2 positive cell per glomerulus cross-section in nicardipine group are lower than in saline group. Conclusion: The degree of injury in glomerular and proteinuria level in Thy1 glomerulonephritis model can be reduced by nicardipine treating. The mechanism was decreased expression of Bcl-2 gene.This study shows that using nicardipine,which can induce apoptosis of mesangial cell in mesangial proliferation glomerulonphritis. It may be a new therapeutic approaches toward glomerular disease designed to harness the power of apoptosis to clear away proliferation of mesangial cells without serous disruption of structure or function.