Clinical And Experiment Research Of The Treatment For DPN By Microsurgical Decompression Combined With DH

Diabetic Peripheral Neuropathy is the primary Diabetic Mellitus complication in nervous system.but lacked of effective treatments.Blood surgar level control,neurotrophy intervention and symptomatic treatment may be the main methods from medical,however,specific surgical managements for DPN is less.In1988,Dellon firstly introduced the surgical treatment for DPN with microsurgical decompression,and then reported the excellent therapeutic efficacy in1992.It became an effective surgical method for DPN from then on.In part I, retrospectively analysed42(50sides)DPN patients underwent microsurgical decompression from3,2004to8,2012. Diagnostic criteria,clinical manifestation,operative indication,operative methods selection,key points during operation,effective rate and recurrence rate were analysed respectively.Results demonstrated that:①.all the28(32sides)patients alleviated their pain and numbness in upper limbs, more than50%patients improved their hands motor function,80%-90%patients recovered their two point discrimination, electrophysiologic monitoring showed the improvement rate was100%,recurrence rate under7%.②.77.7%patients(14/18sides) released their pain and numbness in lower limbs,73.3%(11/15) cases resolved their balance dysfunction.No one get amputation because of DPN during follow-up period.Postopertion evaluation at present depends only on patient self felling,physical examination and electrophysiologic monitoring results.So it is necessary to explore more scientific,objective and precise index to judgement operative effection, for example the nervous microstructure,and animal experiment become the first selection.In prat Ⅱ, we first established the type I diabetic rat models by intraperitoneal injection of STZ (60mg/kg) in male Wistar rats, After successful modeling, the footprint and gait analysis,electrophysiologic examination,nerve fibers density observation in epidermis and right hind tibial nerve tissue staining were performed.Results showing: DPN model preparation time was at least8weeks. Compared with control group:The footprint and gait parameters (PL and ITS) were abnormal in the model group (P<0.05), but there was no significant difference(P>0.05) in TS; The tibial nerve conduction velocity in tarsal tunnel was decreased significantly in the model group (90%rats), compared to0in the control group. The density of nerve fibers of calf epidermal was decreased in the model group. The histopathological examination showed obvious nerve edema,demyelination and axon degeneration.During clinical practice.we fount that the treatment result was better combined microsurgical decompression with DH compared to single surgical treatment.Therefore.in part Ⅲ, we carried out molecular biology experiment to explore the effective mechanism of DH for peripheral nerve. In SC apoptosis experiment,SC were divided into control group、AGEs group and DH+AGEs group, SPSS was used for statistical analysis of cells number. RT-PCR and western blot was used to detect the BDNF mRNA and protein expression. PKC inhibitor PI3K inhibitor、PKA inhibitor、 MEK inhibitor、ERK inhibitor and p38inhibitor were respectively added into the experiment to determine signaling pathways. The Results demonstrated:SC was decreased significantly in AGEs group than control one (P=0.001),but increased in DH+AGEs group than AGEs group (P=0.0006);DH could promote the expression of BDNF mRNA and protein than control one (P=0.00004); compared to control group, BDNF mRNA expression was decreased in DH+Calphostin C grop (P=0.001); all of the BDNF mRNA expression was significantly decreased in DH+U0126. DH+FR180204and DH+SB203580group(P<0.05). The Conclusion was:DH could effectively inhibit SC apoptosis induced by AGEs and significantly promote BDNF expression; PKC and EK/ERK/p38may be the important signaling transconduction pathway for BDNF expression.