C-JNK信号通路对糖尿病大鼠心肌Ito钾通道重构的影响

目的研究c-JNK信号通路在糖尿病(DM)大鼠左室心肌细胞电压门控钾通道(Kv)重构中的作用和内在调控机制。方法将50只健康SD大鼠随机分为DM组[n=25,采用链尿佐菌素(STZ)诱导成模]和对照组(sham)(n=25)。应用全细胞膜片钳方法记录DM组与sham组大鼠心室肌瞬时外向钾电流(Ito);使用非放射性JNK激酶分析kit进行c-Jun活性测定。应用JNK抑制剂SP600125(10M)对DM大鼠心肌细胞进行体外孵育,观察孵育前后心肌细胞Ito的变化。用硫氧还蛋白还原酶(TrxR)抑制剂金诺芬(AF)对经JNK抑制剂SP600125孵育的大鼠心肌细胞进行处理,观察处理前后心肌细胞Ito的变化。应用抗Kv4.2抗体对Kv4.2的含量进行检测,检测结果使用UVP生物成像系统进行分析。结果DM组心肌JNK活性显著升高超过1倍,而Ito显著降低[Sham组:(31.2±3.4)pA/pF,n=16;DM组:(15.4±3.1)pA/pF,n=17;P<0.05]。DM大鼠心室肌细胞经JNK抑制剂SP600125(10 M)处理4 h后,Ito电流密度可恢复至Sham组水平[DM+SP600125组:(31.9±3.8)pA/pF,n=18;Sham组:(31.2±3.4)pA/pF,n=16;P<0.05];且sham组经SP600125处理后的最大Ito电流强度[(29.8±3.4)pA/pF,n=9]和未经处理的sham组无统计学差异。DM心肌经膜渗透性蛋白抑制剂JNKI-1(10 M)处理后,Ito密度也有显著增加,而sham组经相同处理后无改变。TrxR抑制剂AF显著抑制了SP600125对DM大鼠心肌Ito电流的增大作用[DM+AF+SP600125:(15.5±3.2)pA/pF,n=17],而AF对sham组Ito无明显影响。JNK抑制剂SP600125治疗后DM大鼠心肌的Kv4.2蛋白表达量显著增大,尽管未完全恢复到sham组心肌水平,但与先前在DM大鼠心肌所观察到的Ito电流改变一致。而JNK抑制并没有明显改变sham组心肌的Kv4.2蛋白表达量。结论DM大鼠心肌钾通道重构是氧化还原敏感的,可能通过持续性激活c-JNK信号通路促进Ito重构。在DM心肌中,JNK活性显著增高,Kv通道的电流密度降低;抑制JNK信号通路后可显著改善Kv通道重构,这一过程可能被硫氧还原蛋白系统所调控。     

The Relationship Between Nocturnal Blood Pressure and Hemorrhagic Stroke in Chinese Hypertensive Patients

To study the relationship between nocturnal blood pressure (BP) variation and spontaneous intracerebral hemorrhage (ICH) among Chinese hypertensive patients and its clinical significance, the authors retrospectively screened 371 patients with primary hypertension (189 patients with ICH, 182 patients without ICH) in Shanghai and analyzed their demographics, clinical information, nocturnal blood pressure variability and medication. Compared with the control group, the levels of blood glucose, triglycerides, and creatinine were significantly increased in the ICH group, along with a marked reduction in nocturnal BP drop (P<.05). Multivariate logistic regression indicated that blood glucose, creatinine, and nocturnal mean arterial pressure were risk factors for ICH, and the magnitude of nocturnal BP drop was negatively related to the risk for ICH. There was no significant difference in the prevalence of reverse dippers between the large hematoma volume group and the small hematoma volume group (χ²=2.529, P=.112), nor among the patients taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers (χ²=1.981, P=.371). Reverse dipping is associated with the risk for ICH, suggesting that appropriate antihypertensive drug and chronotherapy might be effective to normalize the rhythm of abnormal circadian variation in hypertensive patients.     

Computer-navigated minimally invasive total knee arthroplasty for patients with retained implants in the femur

Total knee arthroplasty (TKA) in patients with knee arthritis and retained implants in the ipsilateral femur is a challenge for knee surgeons. Use of a conventional intramedullary femoral cutting guide is not practical because of the obstruction of the medullary canal by implants. Previous studies have shown that computer-assisted surgery (CAS) can help restore alignment in conventional TKA for patients with knee arthritis with retained femoral implants or extra-articular deformity, without the need for implant removal or osteotomy. However, little has been published regarding outcomes with the use of navigation in minimally invasive surgery (MIS)-TKA for patients with this complex knee arthritis. MIS has been proven to provide less postoperative pain and faster recovery than conventional TKA, but MIS-TKA in patients with retained femoral implants poses a greater risk in limb malalignment. The purpose of this study is to report the outcome of CAS-MIS-TKA in patients with knee arthritis and retained femoral implants. Between April 2006 and March 2008, eight patients with knee arthritis and retained femoral implants who underwent the CAS-MIS-TKA were retrospectively reviewed. Three of the eight patients had extra-articular deformity, including two femur bones and one tibia bone, in the preoperative examination. The anteroposterior, lateral, and long-leg weight-bearing radiographs carried out at 3-month follow-up was used to determine the mechanical axis of lower limb and the position of components. The mean preoperative femorotibial angle in patients without extra-articular deformity was 3.8° of varus and was corrected to 4.6° of valgus. With the use of navigation in MIS-TKA, the two patients in this study with extra-articular femoral deformity also obtained an ideal postoperative mechanical axis within 2° of normal alignment. Overall, there was a good restoration of postoperative mechanical alignment in all cases, with a mean angle of 0.4° of varus. No limb malalignment or component malposition was found. In clinical assessments, there were also significant improvements in knee specific scores, functional scores, and motion arc. The results of this study suggest that navigation can help achieve accurate alignment and proper prosthesis positioning in MIS-TKA for patients with retained femoral implants and for whom intramedullary rod guidance is impractical.