目的 观察冬虫夏草 (CS) 对糖尿病肾病 (DN)大鼠纤溶系统功能的影响.方法 44只大鼠随机分为正常对照组、模型组 (给予链脲佐菌素55 mg/kg体重腹腔注射),CS早期干预组及冬虫夏草晚期干预组,12 w后测体重、肾重、血糖、血肌酐 (Scr)、24 h尿蛋白等指标,光镜观察肾脏病理变化,免疫组化法分别检测组织型纤溶酶原激活物 (t-PA)/纤溶酶原激活物抑制剂表达 (PAI).结果 模型组肾重、血糖、Scr、24 h尿蛋白均明显高于正常对照组(P＜0.01),PAI表达明显高于正常对照组,体重、t-PA表达明显低于正常对照组;两干预组肾重、Scr、血尿素氮 (BUN)、24 h尿蛋白、t-PA表达均高于模型组(P＜0.05),低于正常对照组(P＜0.01),体重、PAI表达低于模型组,高于正常组,血糖较模型组无明显变化;冬虫夏草早期干预组效果优于晚期干预组(P＜0.05).结论 DN时存在t-PA/PAI失衡,冬虫夏草治疗DN的机制之一为矫正t-PA/PAI失衡.

Objective To study the effects of cordyceps sinensis on renal expressions of cathepsin B(CB)and cystatin C(CC)in diabetic nephropathy(DN)rats,and investigate its mechanisms.Methods100 healthy male Wistar rats were divided into normal and diabetic groups.The diabetic rat models were established by intraperitoneal injection of STZ(55 mg/kg),then the diabetic model rats were divided into model and treatment groups.At the end of 4,8 and 16 weeks,the urine of each group rats was collected,then 10 rats of each group were sacrificed and the kidneys and blood of them were collected.The expressions of CB,CC,ColⅣ and fibronectin(FN)in renal tissue were measured by real time PCR and immunohistochemical technique.ResultsCompared with normal group,the levels of Ccr and urine protein excretion of model group and treatment group were increased at 4 weeks(P<0.01),the expressions of CB,CC,ColⅣ and FN were significantly increased at 8 weeks(P<0.01,P<0.05),but the expression of CB in model group at 16 weeks was significantly decreased(P<0.01).Compared with model group,the expressions of CC,ColⅣ and FN in treatment group were significantly decreased at 16 weeks(P<0.01,P<0.05),but the expression of CB was significantly increased(P<0.01).ConclusionsCordyceps sinensis can reduce the excessive accumulation of ECM in the kidney of DN rats through balancing the expressions of CB and CC.

AIM:To observe the expressions of cathepsin B (CB) and cystatin C (CC) in different stage of diabetic rats and to investigates their potential roles.METHODS:Sixty rats were divided into diabetes mellitus group induced by intravenous injection of streptozotocin (55 mg/kg) and normal group injected with citrate buffer. Ten rats were sacrificed respectively at the end of fourth week,eighth week and sixteenth week in both groups. 24 h urine excretion was collected in rats before sacrifice. The blood and the kidney were also collected. The mRNA and protein expressions of CB and CC in kidney were detected by real time PCR and immunohistochemical staining,respectively.RESULTS:At the end of eighth week,the expression of Ccr,24 h urinary protein excretion,CB,CC in diabetic rats increased significantly,compared to the results at the fourth week (P0.01 or P0.05). With the aggravation of diabetic nephropathy,the expressions of CC,colⅣ,FN and 24 h urinary protein excretion were up-regulated significantly (P0.01 or P0.05). The expression of CB in diabetic rats was up-regulated at eighth week significantly (P0.01),whereas,at the end of sixteenth week it was down-regulated significantly (P0.01). The 24 h urinary protein excretion,the expressions of colⅣ at protein and mRNA levels and FN were negatively correlated with CB (P0.01).CONCLUSION:The unbalance of CB and CC exists in diabetic nephropathy renal tissue,which is likely to lead to the accumulation of extracellular matrix.

Objective To observe the effects of cordycepic hypha(cordyceps sinensis,CS)on the pathological changes,the expression of matrix metalloproteinase(MMP)-2 and tissue inhibitor of metalloproteinase(TIMP)-2 in nephridial tissue of diabetic nephropathy(DN)rats and to explore the protective effects of CS and its mechanisms on the kidney.Methods Diabetic rat models were induced by injection of streptozotocin(STZ).These rats were randomly divided into diabetes model,CS 1(5.0 g·kg-1·d-1,given at the onset of DM model)and CS2(5.0 g·kg-1·d-1,given after 4 w)groups.At the same time,negative control group was set up.Plasma glucose,serum creatinine(SCr),blood urea nitrogen(BUN),and 24 h urinary protein(Upro)were observed after 8 weeks.The pathological changes of kidney were observed by light microscopy.The expressions of MMP-2,TIMP-2 and Col Ⅳ were detected in nephridial tissue by immunohistochemical technique.Results Compared with negative control group,the other three groups had significantly higher plasma glucose,Scr,BUN and Upro levels(all P<0.01);MMP-2 expression was decreased significantly in nephridial tissues(P<0.01),but Col Ⅳ as well as TIMP-2 expressions increased(P<0.01).After interfered,compared with DM model group,the above-mentioned abnormal indexes were improved significantly(P<0.05 or P<0.01),except for plasma glucose.CS1 group had better effect than CS2(P<0.05 or P<0.01),except for plasma glucose and BUN.Conclusions CS has some protective effect on the kidney of diabetic rats,which may be related with the inhibition of excessive deposition of glomeruli extracellular matrix by up-regulating MMP-2 and downregulating TIMP-2 expressions.And the earlier treatment,the better effect.