Abstract：Objective ： To investigate the preventive effect of hesperidin （HSP） nanoparticles on diabetic
cardiomyopathy（ DCM） and their mechanism. Methods ： HSP loaded nanoparticles（ HSP-NPs） were prepared
by injection method and their qualities were investigated. The type I diabetes（ DM） animal model was established
by intraperitoneal injection of a single large dose of streptozotocin（ STZ）. The rats were randomly divided into
a normal control group， a DM group， an HSP solution group， and an HSP nanoparticle group， and then received
corresponding forms of drug treatment intervention. After the drug intervention， the cardiac function of rats in
each group was evaluated by ultrasound in vivo， and the pathological characteristics of the cardiac tissue of rats
in each group were evaluated by H-E staining in vitro. ELISA and Western blot analysis were used to evaluate the
mechanisms of HSP preventing DCM. Results ： The HSP-NPs was uniformly dispersed with a encapsulation rate
as high as（ 91.23±5.23）%. Ultrasound heart function test and H-E staining results showed that compared with
the normal control group， LVESD and LVEDD of DM group were significantly increased， LVEF， E/A and LVFS
values were significantly decreased， and the myocardial cells were disordered， and the myocardial fibers were
broken. Compared with DM model and HSP solution group， LVESD and LVEDD values of HSP nanoparticle group
were significantly decreased， LVEF， E/A and LVFS values were significantly increased， the myocardial cells were
arranged regularly， the myocardial tissue was complete ， and the morphology was close to that of normal control rats.
ELISA and Western blotting analysis showed that compared with the normal control group， the contents of SOD，
GSP-Px and Bcl-2 in myocardium of DM group were significantly decreased， and MDA content， caspase-3 and
Bax protein expression were significantly increased.
Compared with the DM group and HSP solution group，
the contents of SOD， GSP-Px and Bcl-2 in myocardium
of rats in HSP nanoparticle group were significantlyhigher， and MDA content， caspase-3 and Bax protein expression were significantly decreased. Conclusion ：
Encapsulation of HSP with nanoparticles can increase the solubility and stability of drug， significantly improve the
bioavailability of drug in vivo， increase the therapeutic effect of HSP， and thus play a role in the prevention of DCM
by inhibiting the apoptosis caused by oxidative stress injury .